炎症性肠病相关易感基因及其作用机制的研究进展

来源期刊：广州医药 | 300-309 发布时间：2025-03-20 收稿时间：2025/4/8 14:28:00 阅读量：171

作者：: 赵雨晨,

黄琛,

关键词：: 炎症性肠病易感基因发病机制; inflammatory bowel disease susceptibility genes pathogenesis

DOI：: 10. 20223 / j. cnki. 1000-8535. 2025. 03. 002

收稿时间：: 2024-10-22
修订日期：
接收日期：
引用总数：: 3

炎症性肠病（IBD）是一种以反复腹痛、腹泻、血便和体重降低为主要表现的慢性特发性性疾病，主要分为溃疡性结肠炎与克罗恩病两种类型。近年来，IBD的患病率随着城市化和工业化进展迅速升高，给中国和全球的公共健康带来沉重的负担。随着人类基因组技术的发展，越来越多的证据表明，遗传学因素在IBD发病过程中起着不可或缺的作用。在亚欧人群中，通过大规模全基因组关联研究现已明确了320个IBD易感基因位点。IBD易感基因在影响机体的细胞代谢、免疫功能调节、肠道上皮屏障和微生物清除等多个方面发挥着重要作用。本文就IBD相关易感基因及其多态性的研究进展进行综述，从基因层面揭示IBD发病的分子机制，并对探索IBD因人而异的个性化治疗方案提供帮助。

黄琛生物学博士，华南理工大学附属第二医院（广州市第一人民医院）副研究员。耶鲁大学医学院博士后，华南理工大学硕士研究生导师。研究方向为免疫相关易感基因介导消化系统疾病进展的分子机制、肠道菌群调控代谢相关脂肪性肝病进展的机制。主持国家自然科学基金青年项目、市科技项目、中央高校项目等多项科研基金，共发表SCI论文22篇，累计影响因子114，他引次数600余次。担任JCTH、JV、Viruses、JMV等杂志审稿人，《广州医药》编委。任广东省医学会微生态医学分会委员、广东省肝病学会肝肠微生态分会委员。

炎症性肠病（inflammatory bowel disease，IBD）以反复腹痛、腹泻、血便和体重降低为主要表现，根据临床表现与治疗手段等不同，主要分为溃疡性结肠炎（ulcerative colitis，UC）与克罗恩病（Crohn’s disease，CD）两种类型，病变可以累及肠道的任何节段，患者病情严重程度不同，缓解和复发常反复交替出现，有时严重到需要住院治疗。流行病学显示，IBD带来的医疗负担在全世界正大幅上升，发展中国家的患病率比发达国家低得多。然而在西方国家中，IBD发病率逐渐趋于平稳，部分新兴工业化发展中国家的发病率却迅速增加^［1］。针对东亚地区，Xu等^［2］以中国全国人口为基础，深入探讨了中国城市地区IBD的疾病分布情况，中国城市的IBD发病率在2016年为每10万人10.04例/年。同时期韩国IBD发病率为每10万人6.9例/年^［3］。中国东部地区的IBD发病率明显高于其他地区，与此同时，中国城市地区的IBD发病率介于新兴工业化国家和西方国家之间。由此可见，随着经济发展与城市工业化水平的提高，IBD已经成为医疗健康领域不可忽视的问题之一。

目前，关于IBD的病因仍存在很大争议，其发病与吸烟等环境风险因素、肠道免疫环境和遗传易感性都存在一定关联。随着核苷酸结合寡聚化结构域2（nucleotide binding oligomerization domain containing 2，NOD2）首次证实与CD相关^［4］，遗传基因在IBD发病中的价值开始被进一步发掘。全基因组关联研究（genome-wide association studies，GWAS）的出现为揭示突变位点、解析遗传背景作出了巨大贡献，有望实现针对特定通路的治疗。除此之外，还出现了全基因组测序（whole-genome sequencing，WGS）、单核苷酸多样性（single nucleotide polymorphisms，SNP）芯片（即免疫芯片）、精细定位（fine-mapping）等多项技术创新^［5］。GWAS分析定位风险相关基因的能力随IBD病例数的增加而逐渐增强，2023年通过一项针对亚洲人群的大规模GWAS，结合30 000多例欧洲血统的IBD病例和对照，Liu等^［6］将IBD易感位点在亚欧人群中的总数扩大到320个。然而，对于存在于非编码区的SNPs——通过影响表观遗传机制改变个体性状，GWAS仍存在一定的局限性。IBD风险基因大多数是UC和CD共有的，但UC和CD无论是临床表现还是遗传学特点仍存在差异。

UC和CD都属于慢性特发性IBD，然其病理现状和受累的肠道节段却不尽相同。CD最常累及末端回肠和近端结肠，病理表现多呈不连续、斑片状、节段性和透壁性。高达20%的患者最初可出现CD的并发症^［7］，如瘘管、脓肿和肠道狭窄，这常常使治疗过程更加复杂。UC常始发于直肠，并连续向结肠近端延伸，病理上较表浅，多局限于黏膜层。IBD不仅影响肠道，还会影响其他身体器官，胃肠道外器官的受累统称为肠外表现（extraintestinal manifestations，EIM）。EIM最常累及肌肉骨骼系统、皮肤、肝胆道和眼睛^［8］。虽然IBD的遗传效应普遍一致，但相比于UC，CD似乎在遗传学方面更为典型^［9］。NOD2作为首个被发现的IBD易感基因，存在多种与CD相关的风险等位基因。自噬相关16样蛋白1（autophagy related 16 like 1，ATG16L1）T300A是ATG16L1最典型的功能缺陷，可以通过改变自噬能力影响CD的发生。TNFRSF14、RFTN2基因主要与UC相关。另有多种基因如人类白细胞抗原（human leukocyte antigen，HLA）、Janus激酶2（Janus kinase 2，JAK2），与UC和CD均存在一定的相关性^［10］。

图 1 韦恩图分析

注：IBD是一种多基因相关的遗传疾病，通过全基因组分析^［10］，

分别列举出了CD、UC以及两者重叠的IBD部分易感基因。

这些基因中大部分在非相关疾病中都显示出相同的作用方向，而CD相关基因蛋白酪氨酸磷酸酶非受体型22（protein tyrosine phosphatase nonreceptor 22，PTPN22）的风险等位基因却在UC中表现出显著的保护作用^［10］。这表明IBD易感基因在疾病的发生中扮演的角色并不完全相同。本文从固有免疫、适应性免疫、肠上皮屏障、微生物清除和代谢等方面解析易感基因参与IBD发病的病理生理学机制。

图 2 易感基因蛋白互作网络图

1 固有免疫

肠道固有免疫作为抵抗病原微生物的第一道防线，主要由中性粒细胞、单核细胞、巨噬细胞、树突状细胞（dendritic cell，DC）等组成，可以通过迅速产生非特异性免疫反应，实现肠道的免疫功能，维持肠道内环境稳态。

1.1 NOD2

NOD2基因位于16q12.1，共有18个外显子，NOD2的功能缺失是CD最大的风险因素^［11］。NOD2在多种细胞内均可表达，包括巨噬细胞、DC、肠上皮细胞（intestinal epithelial cell，IEC）、内皮细胞等。在西方人群中，这三种基因突变rs2066844、rs2066845和rs2066847与近50%的家族性CD病例有关，它们都会损害NOD2配体的识别^［12］。该基因编码的NOD2受体是一种经典的模式识别受体（pattern recognition receptors，PRR），通过识别配体如细菌细胞壁的胞壁酰二肽（muramyl dipeptide，MDP）发挥作用。在出现感染症状时，NOD2可以被细菌激活，并在活化的成纤维细胞中表达。NOD2的缺失驱动CD¹⁴⁺外周血单核细胞异常分化，表达高水平胶原蛋白的成纤维细胞数量异常增加，成纤维细胞-巨噬细胞稳态被打破^［13］。在携带一个NOD2风险等位基因（NOD2^WT/MT）和携带两个NOD2风险等位基因的（NOD2^MT/MT）个体中，研究发现随着NOD2风险等位基因数量增加，活化的成纤维细胞增加^［14］。这些都表明NOD2的缺失无法改善纤维化和炎症状态，并且可能使得CD并发症肠道纤维狭窄风险增加。有研究表明，携带1个突变NOD2等位基因的个体发生CD的风险升高至2~4倍，而携带2个突变NOD2等位基因的个体发生CD的风险升高至15~40倍^［15］。这也证实了NOD2功能缺陷程度的不同对肠道稳态存在差异影响。

1.2 PTPN2

蛋白酪氨酸磷酸酶非受体型2（protein tyrosine phosphatase nonreceptor 2，PTPN2）基因位于18p11.21，共有15个外显子。巨噬细胞中PTPN2缺陷可以减少编码T细胞酪氨酸磷酸酶（T-cell protein tyrosine phosphatase，TCPTP），通过巨噬细胞途径增加了肠上皮屏障的通透性。PTPN2缺陷型巨噬细胞可以表达高水平的CD86，并使白细胞介素-6（interleukin-6，IL-6）分泌增加，增加IBD患病可能性。该基因缺陷型巨噬细胞优先分化为促炎/M1型巨噬细胞，增加对肠上皮屏障的破坏^［16］。而PTPN2相较于巨噬细胞，在粒细胞中表达更多^［9］。PTPN2对粒细胞的数量影响较小，但对粒细胞的功能起至关重要的作用。PTPN2的缺失损伤了粒细胞的细菌杀伤功能，使得细菌更容易移位到肠上皮屏障之外，从而使肠道更容易出现炎症反应^［17］。在DC中，PTPN2缺乏会使肠道固有层中各种免疫细胞的浸润改变，其中巨噬细胞增加明显。Hering等^［18］认为机体可能通过巨噬细胞的增加补偿PTPN2介导的抗炎反应的丧失，从而避免肠道炎症严重程度增加。

2 适应性免疫

与固有免疫相反，适应性免疫系统具有高度特异性，主要参与者是T、B细胞。多种细胞因子也在适应性免疫中起着不可或缺的作用。固有免疫与适应性免疫相辅相成，从而清除入侵的病原体微生物。影响固有免疫的基因可以通过直接或间接的方式进而影响适应性免疫系统。

2.1 IL-23R

促炎细胞因子白细胞介素-23受体（interleukin-23R，IL-23R）基因位于1p31.3，共有14个外显子。IL-23/IL-23R是IL-23/Th17通路的关键组成部分，对UC与CD的发病产生重大影响。IL-23Rrs10889677、rs1004819、rs11209032为重要CD风险性变异，增加CD患病风险^［19］。IL-23由p19亚基和与IL-12共用的p40亚基组成，在自身免疫疾病的发病中起重要作用。在缺乏IL-23p19的小鼠中，T细胞产生的IL-17减少甚至检测不到。这表明IL-23对于自身抗原特异性T细胞产生IL-17至关重要。IL-23还可以促进IL-6、TNF等多种促炎细胞因子的产生，维持肠道的炎症状态。IL-6、IL-23的存在可以诱导Th17细胞的产生，IL-6可以通过促进Th17细胞产生IL-21，进而增加IL-23R数量，通过正反馈回路，实现Th17细胞的扩增^［20］。有报道显示，IL-23p19基因异常表达增加的小鼠出现多器官炎症，可以累及末端回肠和结肠，严重甚至导致死亡^［21］。

2.2 IRF5

干扰素调节因子5（interferon regulatory factor 5，IRF5）基因位于7q32.1，共有13个外显子，该基因编码的IRF5是一种转录因子，与许多慢性炎症疾病有关，包括UC、系统性红斑狼疮、类风湿关节炎等^{［10，22］}。在巨噬细胞中，IRF5会促进细胞因子、趋化因子的表达，为Th1/Th17反应的发生建立了环境条件。小鼠实验表明，体内CD4+ T细胞中的IRF5会增加诱导结肠炎的严重程度，在携带高表达IRF5的人类CD4^+
T细胞中，Th1/Th17细胞因子增加，而Th2相关细胞因子和抗炎因子IL-10、TGF-β降低^［23］。这在很大程度上是通过IRF5功能改变的髓系细胞充当抗原呈递细胞，进而对T细胞产生影响^［24］。Brune等^［25］探索了IRF5在T细胞内部的功能，特别是在Th17中，揭示了一种导致异常免疫反应的刺激依赖性T细胞内部缺陷。此外，T细胞中IRF5也通过调节趋化因子途径促进T细胞运输到淋巴结发挥作用^［23］。

3 肠上皮屏障

肠上皮屏障（intestinal epithelial barrier，IEB）不仅将腔内细菌与黏膜免疫系统分隔开，而且还可以通过促进多种免疫反应维持肠上皮稳态。除了IEC构建的化学和体液屏障外，细胞之间还通过顶端连接复合体（apical junctional complex，AJC）建立了物理屏障。在已经发现的易感基因位点内，许多突变通过调节IEC与肠道微生物的相互作用、肠道自身免疫等，使得IEB功能发生改变，增加IBD易感性。

3.1 CDH1

钙黏蛋白1（cadherin 1，CDH1）基因位于16q22.1，共有16个外显子，该基因编码钙黏蛋白超家族中的E-钙黏蛋白（E-cadherin）。突变被广泛认为对多种癌症有致病作用，如胃癌、乳腺癌等^［26-27］，通过影响细胞黏附和迁移，促进肿瘤的浸润与转移。紧密连接（tight junction，TJ）是细胞间连接的重要组成部分，由claudins、occludin等跨膜蛋白，Zonula Occludens（ZO）外围膜蛋白等多种蛋白组成。CDH1表达的E-cadherin，是TJ形成所必需的，在维持肠黏膜屏障中也起着十分重要的作用，通过调节TJ的结合来促进表皮屏障的形成^［28］。E-cadherin的减少显著增加了肠上皮的通透性。

3.2 HNF4A

肝细胞核因子4α（hepatocyte nuclear factor 4 alpha，HNF-4α）基因位于20q13.12，共有15个外显子，该基因编码HNF-4α是一种转录因子，在肠道的发育中起重要作用。在HNF-4α缺失的小鼠中TJ的表达发生巨大变化，claudin 4和7以及 ZO-1在mRNA水平显著降低，而 claudin 2显著增加^［29］。有研究表明，claudin 2表达的增加是导致屏障功能障碍的原因^［30］。claudins负责TJ的门控功能，而TJ控制旁细胞通透性。HNF-4α缺失的情况下，TJ扩张，旁细胞通透性增加^［29］。之前确诊为IBD的患者中，有接近40%的CD患者出现旁细胞通透性增加^［31］。刷状缘由紧密排列的微绒毛组成，IEC通过这种结构来扩大上皮表面积，进而实现肠道功能。基因集富集分析表明，当HNF-4α缺失时，刷状缘基因在肠道中下调。小鼠实验进一步证实，刷状缘标记物的表达，如碱性磷酸酶、β-肌动蛋白、绒毛蛋白和Ezrin蛋白在肠道HNF-4α丢失后均受到严重破坏^［32］。维持上皮屏障功能和促进其修复的机制也是肠道发挥和维持其功能的有效保障。通过辐射损伤体外肠类器官，研究者发现缺乏HNF-4的类器官无法在体外增殖。在肠道HNF-4α基因敲除的小鼠中，再次观察到肠道再生受损^［33］。这有可能成为IBD发病严重程度增加的原因之一。

3.3 SLC26A3

溶质载体家族26成员3（solute carrier family 26 member 3，SLC26A3）基因位于7q22.3-q31.1，共有21个外显子，该基因编码的蛋白质是一种跨膜糖蛋白Cl^- /HCO₃ ^-离子转运蛋白，也称为腺瘤下调蛋白（downregulated in adenoma，DRA），于肠道氯离子的吸收至关重要。DRA位于肠道黏膜，特别是柱状上皮的顶端膜和一些杯状细胞。SLC26A3于2009年首次被鉴定为参与UC发病机制的重要基因^［34］。一项我国的人群研究显示，SLC26A3基因rs2108225位点变异可能会使患UC的风险大大增加，而rs17154444位点变异可能导致UC严重程度的不同^［35］。DRA的缺失使HCO₃ ^-分泌严重降低，结肠液体吸收减少，缺乏牢固黏附的黏液层^［36］。除了参与肠道中的液体电解质吸收、酸碱平衡以及黏液屏障外，DRA 还参与上皮屏障的构成。SLC26A3在结肠顶端膜上高度表达，并对TJ的表达产生影响。在缺少DRA的细胞中，F-肌动蛋白附着明显减弱，occludin、claudin 1和claudin 5的表达水平显著降低，而claudin 2的表达较高^［37］。除了TJ外，黏附连接（adherens junction，AJ）对维持上皮完整也十分重要。在缺少DRA的细胞中，关键AJ如E-cadherin以及协助其发挥作用的β-catenin表达显著降低^［38］。这样的变化可能会对上皮来源的细胞因子和信号分子的分泌产生不利影响，从而影响肠道上皮屏障稳态。Jayawardena等^［39］研究表明，DRA的缺失通过诱导IL-33的释放，促使2型免疫细胞活化，通过过度免疫增加UC的易感性。

4 微生物清除

自噬是细胞代谢过程之一，可以导致溶酶体介导的细胞器和蛋白质聚集体的再循环，以及细胞内病原体的破坏。自噬缺陷可能通过破坏肠道稳态、影响肠道菌群、损害细胞内细菌清除等维持肠道炎症状态，对IBD的发生产生严重影响。

4.1 ATG16L1

ATG16L1基因位于2q37.1，共有19个外显子，该基因编码的蛋白质参与组成自噬必需的蛋白质复合物。过去多个GWAS表明，ATG16L1与CD的发病有着极大关联，经典变异发生在rs2241880，ATG16L1 T300A蛋白质300位的苏氨酸被丙氨酸取代^［40］。ATG16L1的缺失选择性作用于CD患者的潘氏细胞（Paneth cell，PC）。每个小肠隐窝平均有5~12个PCs，细胞顶端颗粒在细菌等刺激下可释放到隐窝腔，导致肠腔中溶菌酶、抗菌肽等物质浓度增加，增加肠道的细菌防御功能^［41］。ATG16L1的功能受损会导致上述关键外泌蛋白的分泌失调，并使胞吐受到抑制，对抵御微生物入侵的IEC产生不利影响^［42］。ATG16L1 T300A显著增加了胱天蛋白酶3（caspase 3，CASP3）和7介导的蛋白质裂解，导致ATG16L1 T300A 蛋白稳定性下降，影响抗菌自噬。在CD患者中，ATG16L1 T300A的纯合体使DC成熟过程中调节自噬的能力丧失，而在杂合体的CD患者中没有出现，表明ATG16L1存在基因剂量依赖性效应^［43］。过去有研究表明，缺失WD40结构域的ATG16L1完全有能力维持经典自噬^［44］。近期Boada-Romero等^［45］发现，WD40对于非典型自噬至关重要，T300A 突变通过降低WD40与TMEM59结合的能力，从而损害细胞对细菌感染的先天防御能力。但对IL-10RB的相互作用和IL-10RB的功能没有影响^［46］。

4.2 IRGM

免疫相关GTP酶家族M（immunity related GTPase M，IRGM）基因位于5q33.1，共有5个外显子，该基因编码的免疫相关GTPase M是一种重要的自噬蛋白，可以通过连接自噬和炎症，维持免疫稳态。IRGM的表达降低会通过干扰介导环鸟苷酸-腺苷酸合成酶（cyclic GMP-AMP synthase，CGAS）、视黄酸诱导型基因I受体（DExD/H-box helicase 58，DDX58）和Toll样受体3（Toll-like receptor 3，TLR3）的自噬降解来影响I型干扰素（interferon，IFN）传导，导致炎症细胞因子增加。IRGM 缺乏还会导致线粒体自噬通量减少、失效线粒体积聚以及线粒体活性氧（mitochondrial reactive oxygen species，mtROS）的增加^［47］。线粒体在IFN-γ的刺激下将线粒体DNA（mitochondrial DNA，mtDNA）释放到细胞质中^［48］， mtDNA充当损伤相关分子模式（damage-associated molecular pattern，DAMP）并被PRRs识别^［49］，通过环鸟苷酸-腺苷酸合成酶-干扰素基因刺激因子通路（cGAS-STING）信号传导、炎症小体激活或Toll样受体9（Toll-like receptor 9，TLR9）信号传导中的任何一种^［50］，引发I型IFN反应，导致自身免疫疾病的发生。NLRP3是一种先天免疫传感器，在病原体相关分子模式（pathogen-associated molecular patterns，PAMP）、DAMP的作用下，使促炎性细胞因子释放增加^［51］，诱导炎症细胞死亡，导致DAMP的释放，DAMP在反馈回路中进一步刺激产生更多的炎性因子，引发恶性循环^［52］。IRGM的缺失阻碍NLRP3炎症小体的活化和组装，并影响p62依赖的NLRP3炎症小体的选择性自噬^［51］，增加了CD的易感性。有研究表明，在伊朗患者中，ATG16L1与CD相关，而IRGM并非伊朗地区CD的易感因素^［53］，同样在加拿大儿童中也发现了这一点^［54］。这表明基因多态性在不同人群、不同地区的影响不同，为后续治疗方法的研究提供了不同思路。除了ATG16L1、IRGM外，LRRK、ULK1、ATG9A、NDP52和ATG4C等多种基因^［55-56］也参与了CD的自噬过程。

5 代谢

近年来，随着基因组学和代谢组学研究的进展，人们逐渐认识到代谢变化在IBD的发病过程中也扮演着重要角色。研究表明，IBD患者存在尿酸代谢、胆汁酸代谢、氨基酸等代谢异常。同时，在IBD发病期间，肠道处于炎性环境中，水肿、血管收缩和血管炎的发生会限制上皮细胞的血液供应，从而导致氧的供需失衡，这是导致组织损伤加剧的一大原因。细菌清除受损、细胞因子分泌改变等引起免疫代谢失调同样也会加重炎症反应。

5.1 HIF1A

缺氧诱导因子-1α（hypoxia inducible factor-1 subunit alpha，HIF1A）基因位于14q23.2，共有16个外显子。HIF1A的表达产物缺氧诱导因子1α（hypoxia inducible factor-1 subunit alpha，HIF-1α）与HIF-1β是HIF-1异源二聚体的来源，可以促进低氧水平下的代谢适应。常氧条件下，脯氨酰羟化酶2（prolyl hydroxylase domain 2，PHD2）和抑制缺氧诱导因子的FIH1共同作用，使HIF-1α蛋白通过泛素-蛋白酶体途径快速降解。而在缺氧条件下，HIF-1与缺氧反应元件结合，启动下游基因的转录^［57］。

过去的研究表明，IEC是缺氧的主要靶点。Cramer等^［58］证明了髓系 HIF-1α可以驱动免疫细胞功能，在炎症条件下，缺乏髓系细胞等的HIF-1α无法上调糖酵解代谢。Bácker等^［59］在2017年的研究提出，在HIF-1α缺陷的动物中，DSS诱导的结肠炎期间主要由于免疫细胞的浸润较低，导致炎症反应水平降低，而Kerber等^［57］在小鼠髓系细胞敲除HIF-1α后在结肠观察到更轻的炎症反应，也证实了上述结论。HIF-1α在不同细胞中的功能也存在差异，在髓系细胞中HIF-1α的条件性敲除可以减轻小鼠结肠炎严重程度，而在DC、T细胞和IEC^［60］中敲除HIF-1α却观察到更严重的症状。

5.2 LACC1

含漆酶结构域的蛋白1（L a c c a s e d o m ai n containing 1，LACC1）基因位于13q14.11，共有9个外显子，是CD、麻风病、特发性关节炎等多种疾病的共同风险基因^［61］。研究者在沙特阿拉伯人中首次发现，LACC1罕见错义突变导致第284位的精氨酸被半胱氨酸取代与早发CD有关。而欧洲常见的SNP rs3764147导致254位的缬氨酸被异亮氨酸取代，该Ile254Val变异体导致LACC1功能丧失，细胞因子分泌减少、细菌清除能力下降等免疫反应缺陷，增加CD风险^［62］。

微生物清除在肠道免疫稳态中起着关键作用，细菌清除受损会大大增加IBD患病风险。LACC1在结肠炎的发病过程中，通过影响细菌清除和细胞因子的产生，从而调节免疫代谢。LACC1在髓系细胞中发挥着重要作用，内质网应激对巨噬细胞中PRRs诱导的结果至关重要^［63］。在PRRs的作用下，巨噬细胞通过诱导产生mtROS、活性氧（reactive oxygen species，ROS）、活性氮（reactive nitrogen species，RNS）等多种途径^［64-65］改善细菌的清除，并通过影响DC，改变对T细胞分化的调节能力，使IFN-γ和IL-17的分泌减少，而Th2型细胞因子如IL-4、IL-5和IL-13的分泌增加，进一步加重炎性反应。此外，LACC1增强PRRs诱导的MAPK和NF-κB信号通路的激活，而这些信号通路又协同作用，诱导依赖LACC1的抗菌通路，加强细菌清除能力^［65］。有氧糖酵解是M1巨噬细胞产生ATP的主要机制，而M2巨噬细胞则依靠线粒体脂肪酸氧化（fatty acid oxidation，FAO，也称β-氧化）来促进氧化磷酸化^［66］。LACC1表达的蛋白质FAMIN，通过与脂肪酸合成酶形成复合物，加速脂肪酸的从头合成，同时促进脂肪酸氧化和糖酵解，为细胞提供更多能量^［62］。然而，不同的风险位点参与疾病的机制尚未完全清楚，或许存在新的基因产物能够通过揭示新的生物学机制，完善和发展LACC1在IBD中的作用。

6 易感基因治疗价值

IBD发病的确切机制尚未完全清楚，大量的基因位点也只能解释疾病的一小部分差异^［10］。然而，遗传学研究在IBD的诊断和治疗中仍扮演着至关重要的角色。首先，易感基因的发现为疾病风险预测提供途径，通过实施早期筛查，我们可以在疾病发展的初期阶段进行干预，从而降低易感人群错过治疗时机的风险。对具有家族遗传史的高危人群，建议尽早干预，减少疾病的发生可能。其次，易感基因的研究有助于对患者进行精确的疾病分型和风险评估，从而指导靶向治疗药物的选择，进而实现个性化医疗。再次，这些易感基因也为评估疾病的严重程度和预后提供了重要工具。最后，易感基因的研究不仅有助于理解IBD的发病机制，还可能揭示新的治疗靶点为开发新的治疗方法提供了可能。IBD易感基因数目庞大，在其他免疫系统疾病的发病中也起到了一定作用，深入探究这些易感基因的致病机制以及关键分子的发掘，有助于我们深入了解IBD，并为制定创新性治疗方案奠定了基础。

1、KAPLAN%E2%80%83G%E2%80%83G%EF%BC%8CWINDSOR%E2%80%83J%E2%80%83W%EF%BC%8EThe%E2%80%83four%E2%80%83epidemiological%E2%80%83%0Astages%E2%80%83in%E2%80%83the%E2%80%83global%E2%80%83evolution%E2%80%83of%E2%80%83inflammatory%E2%80%83%20bowel%E2%80%83%0Adisease%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Rev%E2%80%83Gastroenterol%E2%80%83Hepatol%EF%BC%8C%0A2021%EF%BC%8C18%EF%BC%881%EF%BC%89%EF%BC%9A56-66%EF%BC%8E

2、XU%E2%80%83L%EF%BC%8CHE%E2%80%83B%EF%BC%8CSUN%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EI%20n%20ci%20d%20e%20n%20c%20e%E2%80%83%20of%E2%80%83%0Ainflammatory%E2%80%83bowel%E2%80%83disease%E2%80%83in%E2%80%83urban%E2%80%83China%EF%BC%9AA%E2%80%83%0Anationwide%E2%80%83population-based%E2%80%83study%EF%BC%BBJ%EF%BC%BD%EF%BC%8EClin%E2%80%83%0AGastroenterol%E2%80%83Hepatol%EF%BC%8C2023%EF%BC%8C21%EF%BC%8813%EF%BC%89%EF%BC%9A3379-%0A3386%EF%BC%8Ee29%EF%BC%8E

3、PARK%E2%80%83S%E2%80%83H%EF%BC%8EUpdate%E2%80%83on%E2%80%83the%E2%80%83epidemiology%E2%80%83of%E2%80%83inflammatory%E2%80%83%0Abowel%E2%80%83disease%E2%80%83in%E2%80%83Asia%EF%BC%9AWhere%E2%80%83are%E2%80%83we%E2%80%83now%EF%BC%9F%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AIntest%E2%80%83Res%EF%BC%8C2022%EF%BC%8C20%EF%BC%882%EF%BC%89%EF%BC%9A159-164%EF%BC%8E

4、HUGOT%E2%80%83J%E2%80%83P%EF%BC%8CCHAMAILLARD%E2%80%83M%EF%BC%8CZOUALI%E2%80%83H%EF%BC%8Cet%E2%80%83%0Aal%EF%BC%8EAssociation%E2%80%83of%E2%80%83NOD2%E2%80%83leucine-rich%E2%80%83%20repeat%E2%80%83variants%E2%80%83%0Awith%E2%80%83susceptibility%E2%80%83to%E2%80%83Crohn%E2%80%99s%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENature%EF%BC%8C%0A2001%EF%BC%8C411%EF%BC%886837%EF%BC%89%EF%BC%9A599-603%EF%BC%8E

5、ANNESE%E2%80%83V%EF%BC%8EGenetics%E2%80%83and%E2%80%83epigenetics%E2%80%83of%E2%80%83IBD%EF%BC%8E%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0APharmacol%E2%80%83Res%EF%BC%8C2020%EF%BC%88159%EF%BC%89%EF%BC%9A104892%EF%BC%8E

6、LIU%E2%80%83Z%EF%BC%8CLIU%E2%80%83R%EF%BC%8CGAO%E2%80%83H%EF%BC%8Cet%E2%80%83al%EF%BC%8EGenetic%E2%80%83architecture%E2%80%83%0Aof%E2%80%83the%E2%80%83inflammatory%E2%80%83bowel%E2%80%83diseases%E2%80%83across%E2%80%83East%E2%80%83Asian%E2%80%83%0Aand%E2%80%83European%E2%80%83ancestries%EF%BC%8E%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Genet%EF%BC%8C2023%EF%BC%8C%0A55%EF%BC%885%EF%BC%89%EF%BC%9A796-806%EF%BC%8E

7、LO%E2%80%83B%EF%BC%8CVESTER-ANDERSEN%E2%80%83M%E2%80%83K%EF%BC%8CVIND%E2%80%83I%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AChanges%E2%80%83in%E2%80%83disease%E2%80%83behaviour%E2%80%83and%E2%80%83location%E2%80%83in%E2%80%83patients%E2%80%83%0Awith%E2%80%83Crohn%E2%80%99s%E2%80%83disease%E2%80%83after%E2%80%83seven%E2%80%83years%E2%80%83of%E2%80%83follow-up%EF%BC%9A%0AA%E2%80%83Danish%E2%80%83population-based%E2%80%83inception%E2%80%83cohort%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83%0ACrohns%E2%80%83Colitis%EF%BC%8C2018%EF%BC%8C12%EF%BC%883%EF%BC%89%EF%BC%9A265-272%EF%BC%8E

8、ROGLER%E2%80%83G%EF%BC%8CSINGH%E2%80%83A%EF%BC%8CKAVANAUGH%E2%80%83A%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AExtraintestinal%E2%80%83%20manifestations%E2%80%83%20of%E2%80%83%20inflammatory%E2%80%83%0Abowel%E2%80%83disease%EF%BC%9ACurrent%E2%80%83concepts%EF%BC%8Ctreatment%EF%BC%8Cand%E2%80%83implications%E2%80%83for%E2%80%83disease%E2%80%83management%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AGastroenterology%EF%BC%8C2021%EF%BC%8C161%EF%BC%884%EF%BC%89%EF%BC%9A1118-1132%EF%BC%8E

9、BONI%E2%80%83C%EF%BC%8CSORIO%E2%80%83C%EF%BC%8ECurrent%E2%80%83views%E2%80%83on%E2%80%83the%E2%80%83interplay%E2%80%83%0Abetween%E2%80%83tyrosine%E2%80%83kinases%E2%80%83and%E2%80%83phosphatases%E2%80%83in%E2%80%83chronic%E2%80%83%0Amyeloid%E2%80%83leukemia%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECancers%EF%BC%8C2021%EF%BC%8C1%203%0A%EF%BC%8810%EF%BC%89%EF%BC%9A2311%EF%BC%8E

10、%E2%80%83%20JOSTINS%E2%80%83L%EF%BC%8CRIPKE%E2%80%83S%EF%BC%8CWEERSMA%E2%80%83R%E2%80%83K%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AHost-microbe%E2%80%83interactions%E2%80%83%20have%E2%80%83%20shaped%E2%80%83the%E2%80%83%20genetic%E2%80%83%0Aarchitecture%E2%80%83of%E2%80%83inflammatory%E2%80%83bowel%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ANature%EF%BC%8C2012%EF%BC%8C491%EF%BC%887422%EF%BC%89%EF%BC%9A119-124%EF%BC%8E

11、SAZONOVS%E2%80%83A%EF%BC%8CSTEVENS%E2%80%83C%E2%80%83R%EF%BC%8CVENKATARAMAN%E2%80%83%0AG%E2%80%83R%EF%BC%8Cet%E2%80%83al%EF%BC%8ELarge-scale%E2%80%83sequencing%E2%80%83identifies%E2%80%83multiple%E2%80%83%0Agenes%E2%80%83and%E2%80%83rare%E2%80%83variants%E2%80%83associated%E2%80%83with%E2%80%83Crohn%E2%80%99s%E2%80%83disease%E2%80%83%0Asusceptibility%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Genet%EF%BC%8C2022%EF%BC%8C54%EF%BC%889%EF%BC%89%EF%BC%9A%0A1275-1283%EF%BC%8E

12、%E2%80%83%20GAO%E2%80%83J%EF%BC%8CZHAO%E2%80%83X%EF%BC%8CHU%E2%80%83S%EF%BC%8Cet%E2%80%83al%EF%BC%8EGut%E2%80%83%20microbial%E2%80%83%0ADL-endopeptidase%E2%80%83alleviates%E2%80%83Crohn%E2%80%99s%E2%80%83disease%E2%80%83via%E2%80%83the%E2%80%83%0ANOD2%E2%80%83pathway%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%E2%80%83Host%E2%80%83Microbe%EF%BC%8C2022%EF%BC%8C30%0A%EF%BC%8810%EF%BC%89%EF%BC%9A1435-1449%EF%BC%8Ee9%EF%BC%8E

13、%E2%80%83HEGARTY%E2%80%83L%E2%80%83M%EF%BC%8CJONES%E2%80%83G%E2%80%83R%EF%BC%8CBAIN%E2%80%83C%E2%80%83C%EF%BC%8E%0AMacrophages%E2%80%83in%E2%80%83intestinal%E2%80%83homeostasis%E2%80%83and%E2%80%83inflammatory%E2%80%83%0Abowel%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Rev%E2%80%83Gastroenterol%E2%80%83Hepatol%EF%BC%8C%0A2023%EF%BC%8C20%EF%BC%888%EF%BC%89%EF%BC%9A538-553%EF%BC%8E

14、%E2%80%83%20NAYAR%E2%80%83S%EF%BC%8CMORRISON%E2%80%83J%E2%80%83K%EF%BC%8CGIRI%E2%80%83M%EF%BC%8Cet%E2%80%83al%EF%BC%8EA%E2%80%83%0Amyeloid%E2%80%93stromal%E2%80%83niche%E2%80%83and%E2%80%83gp130%E2%80%83rescue%E2%80%83in%E2%80%83NOD2-%0Adriven%E2%80%83Crohn%E2%80%99s%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENature%EF%BC%8C2021%EF%BC%8C593%0A%EF%BC%887858%EF%BC%89%EF%BC%9A275-281%EF%BC%8E

15、EL%E2%80%83HADAD%E2%80%83J%EF%BC%8CSCHREINER%E2%80%83P%EF%BC%8CVAVRICKA%E2%80%83S%E2%80%83R%EF%BC%8Cet%E2%80%83%0Aal%EF%BC%8EThe%E2%80%83genetics%E2%80%83of%E2%80%83inflammatory%E2%80%83bowel%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AMol%E2%80%83Diagn%E2%80%83Ther%EF%BC%8C2024%EF%BC%8C28%EF%BC%881%EF%BC%89%EF%BC%9A27-35%EF%BC%8E

16、SPALINGER%E2%80%83M%E2%80%83R%EF%BC%8CSAYOC-BECERRA%E2%80%83A%EF%BC%8CSANTOS%E2%80%83%0AA%E2%80%83N%EF%BC%8Cet%E2%80%83al%EF%BC%8EPTPN2%E2%80%83%20regulates%E2%80%83interactions%E2%80%83%20between%E2%80%83%0Amacrophages%E2%80%83and%E2%80%83intestinal%E2%80%83epithelial%E2%80%83cells%E2%80%83to%E2%80%83promote%E2%80%83%0Aintestinal%E2%80%83barrier%E2%80%83function%EF%BC%BBJ%EF%BC%BD%EF%BC%8EGastroenterology%EF%BC%8C%0A2020%EF%BC%8C159%EF%BC%885%EF%BC%89%EF%BC%9A1763-1777%EF%BC%8Ee14%EF%BC%8E

17、SPALINGER%E2%80%83M%E2%80%83R%EF%BC%8CSCHWARZFISCHER%E2%80%83M%EF%BC%8C%0ANIECHCIAL%E2%80%83A%EF%BC%8Cet%E2%80%83al%EF%BC%8ELoss%E2%80%83%20of%E2%80%83%20PTPN22%E2%80%83%20promotes%E2%80%83%0Aintestinal%E2%80%83inflammation%E2%80%83by%E2%80%83compromising%E2%80%83granulocyte%02mediated%E2%80%83antibacterial%E2%80%83defence%EF%BC%8E%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83%20Crohns%E2%80%83%0AColitis%EF%BC%8C2021%EF%BC%8C15%EF%BC%8812%EF%BC%89%EF%BC%9A2118-2130%EF%BC%8E

18、HERING%E2%80%83L%EF%BC%8CKATKEVICIUTE%E2%80%83E%EF%BC%8CSCHWARZFISCHER%E2%80%83%0AM%EF%BC%8Cet%E2%80%83al%EF%BC%8EMacrophages%E2%80%83compensate%E2%80%83for%E2%80%83loss%E2%80%83of%E2%80%83protein%E2%80%83%0Atyrosine%E2%80%83%20phosphatase%E2%80%83N2%E2%80%83in%E2%80%83%20dendritic%E2%80%83cells%E2%80%83to%E2%80%83%20protect%E2%80%83%0Afrom%E2%80%83elevated%E2%80%83colitis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EInt%E2%80%83J%E2%80%83Mol%E2%80%83Sci%EF%BC%8C2021%EF%BC%8C22%0A%EF%BC%8813%EF%BC%89%EF%BC%9A6820%EF%BC%8E

19、XU%E2%80%83W%E2%80%83D%EF%BC%8CXIE%E2%80%83Q%E2%80%83B%EF%BC%8CZHAO%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EAssociation%E2%80%83%0Aof%E2%80%83%20Interleukin-23%E2%80%83%20receptor%E2%80%83gene%E2%80%83%20polymorphisms%E2%80%83with%E2%80%83%0Asusceptibility%E2%80%83to%E2%80%83Crohn%E2%80%99s%E2%80%83disease%EF%BC%9AA%E2%80%83meta-analysis%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8ESci%E2%80%83Rep%EF%BC%8C2015%EF%BC%885%EF%BC%89%EF%BC%9A18584%EF%BC%8E

20、ZHOU%E2%80%83L%EF%BC%8CIVANOV%E2%80%83I%E2%80%83I%EF%BC%8CSPOLSKI%E2%80%83R%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AIL-6%E2%80%83programs%E2%80%83T%EF%BC%88H%EF%BC%89-17%E2%80%83%20cell%E2%80%83%20differentiation%E2%80%83%20by%E2%80%83%0Apromoting%E2%80%83sequential%E2%80%83engagement%E2%80%83of%E2%80%83the%E2%80%83IL-21%E2%80%83and%E2%80%83IL-%0A23%E2%80%83pathways%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Immunol%EF%BC%8C2007%EF%BC%8C8%EF%BC%889%EF%BC%89%EF%BC%9A%0A967-974%EF%BC%8E

21、VERSTOCKT%E2%80%83B%EF%BC%8CSALAS%E2%80%83A%EF%BC%8CSANDS%E2%80%83B%E2%80%83E%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AIL-12%E2%80%83and%E2%80%83%20IL-23%E2%80%83pathway%E2%80%83inhibition%E2%80%83in%E2%80%83inflammatory%E2%80%83%0Abowel%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Rev%E2%80%83Gastroenterol%E2%80%83Hepatol%EF%BC%8C%0A2023%EF%BC%8C20%EF%BC%887%EF%BC%89%EF%BC%9A433-446%EF%BC%8E

22、EAMES%E2%80%83H%E2%80%83L%EF%BC%8CCORBIN%E2%80%83A%E2%80%83L%EF%BC%8CUDALOVA%E2%80%83I%E2%80%83A%EF%BC%8E%0AInterferon%E2%80%83%20regulatory%E2%80%83factor%E2%80%835%E2%80%83in%E2%80%83human%E2%80%83autoimmunity%E2%80%83%0Aand%E2%80%83murine%E2%80%83models%E2%80%83of%E2%80%83autoimmune%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ATransl%E2%80%83Res%EF%BC%8C2016%EF%BC%8C167%EF%BC%881%EF%BC%89%EF%BC%9A167-182%EF%BC%8E

23、YAN%E2%80%83J%EF%BC%8CPANDEY%E2%80%83S%E2%80%83P%EF%BC%8CBARNES%E2%80%83B%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8ET%E2%80%83cell%02intrinsic%E2%80%83IRF5%E2%80%83regulates%E2%80%83T%E2%80%83cell%E2%80%83signaling%EF%BC%8Cmigration%EF%BC%8C%0Aand%E2%80%83differentiation%E2%80%83and%E2%80%83promotes%E2%80%83intestinal%E2%80%83inflammation%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%E2%80%83Rep%EF%BC%8C2020%EF%BC%8C31%EF%BC%8813%EF%BC%89%EF%BC%9A107820%EF%BC%8E

24、YAN%E2%80%83J%EF%BC%8CHEDL%E2%80%83M%EF%BC%8CABRAHAM%E2%80%83C%EF%BC%8EMyeloid%E2%80%83cell%02intrinsic%E2%80%83%20IRF5%E2%80%83%20promotes%E2%80%83%20T%E2%80%83%20cell%E2%80%83%20responses%E2%80%83through%E2%80%83%0Amultiple%E2%80%83distinct%E2%80%83checkpoints%E2%80%83in%E2%80%83vivo%EF%BC%8Cand%E2%80%83%20IRF5%E2%80%83%0Aimmune-mediated%E2%80%83disease%E2%80%83risk%E2%80%83variants%E2%80%83modulate%E2%80%83these%E2%80%83%0Amyeloid%E2%80%83cell%E2%80%83functions%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJ%E2%80%83Immunol%EF%BC%8C2020%EF%BC%8C205%0A%EF%BC%884%EF%BC%89%EF%BC%9A1024-1038%EF%BC%8E

25、BRUNE%E2%80%83Z%EF%BC%8CRICE%E2%80%83M%E2%80%83R%EF%BC%8CBARNES%E2%80%83B%E2%80%83J%EF%BC%8EPotential%E2%80%83T%E2%80%83%0Acell-intrinsic%E2%80%83%20regulatory%E2%80%83%20roles%E2%80%83for%E2%80%83%20IRF5%E2%80%83via%E2%80%83cytokine%E2%80%83%0Amodulation%E2%80%83in%E2%80%83%20T%E2%80%83%20helper%E2%80%83%20subset%E2%80%83%20differentiation%E2%80%83%20and%E2%80%83%0Afunction%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83Immunol%EF%BC%8C2020%EF%BC%8811%EF%BC%89%EF%BC%9A1143%EF%BC%8E

26、MASSARI%E2%80%83G%EF%BC%8CMAGNONI%E2%80%83F%EF%BC%8CFAVIA%E2%80%83G%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AFrequency%E2%80%83of%E2%80%83CDH1%E2%80%83germline%E2%80%83mutations%E2%80%83in%E2%80%83non-gastric%E2%80%83%0Acancers%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECancers%EF%BC%8C2021%EF%BC%8C13%EF%BC%8810%EF%BC%89%EF%BC%9A2321%EF%BC%8E

27、GREGORY%E2%80%83S%E2%80%83N%EF%BC%8CDAVIS%E2%80%83J%E2%80%83L%EF%BC%8ECDH1%E2%80%83and%E2%80%83hereditary%E2%80%83%0Adiffuse%E2%80%83gastric%E2%80%83cancer%EF%BC%9AA%E2%80%83narrative%E2%80%83review%EF%BC%BBJ%EF%BC%BD%EF%BC%8EChin%E2%80%83%0AClin%E2%80%83Oncol%EF%BC%8C2023%EF%BC%8C12%EF%BC%883%EF%BC%89%EF%BC%9A25%EF%BC%8E

28、LESSEY%E2%80%83L%E2%80%83R%EF%BC%8CROBINSON%E2%80%83S%E2%80%83C%EF%BC%8CCHAUDHARY%E2%80%83R%EF%BC%8C%0Aet%E2%80%83al%EF%BC%8EAdherens%E2%80%83junction%E2%80%83proteins%E2%80%83on%E2%80%83the%E2%80%83move-From%E2%80%83%0Athe%E2%80%83membrane%E2%80%83to%E2%80%83the%E2%80%83nucleus%E2%80%83in%E2%80%83intestinal%E2%80%83diseases%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AFront%E2%80%83Cell%E2%80%83Dev%E2%80%83Biol%EF%BC%8C2022%EF%BC%8810%EF%BC%89%EF%BC%9A998373%EF%BC%8E

29、VEMURI%E2%80%83K%EF%BC%8CRADI%E2%80%83S%E2%80%83H%EF%BC%8CSLADEK%E2%80%83F%E2%80%83M%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AMultiple%E2%80%83%20roles%E2%80%83%20and%E2%80%83%20regulatory%E2%80%83%20mechanisms%E2%80%83%20of%E2%80%83%20the%E2%80%83%0Atranscription%E2%80%83factor%E2%80%83HNF4%E2%80%83in%E2%80%83the%E2%80%83intestine%EF%BC%BBJ%EF%BC%BD%EF%BC%8EFront%E2%80%83%0AEndocrinol%EF%BC%8C2023%EF%BC%8814%EF%BC%89%EF%BC%9A1232569%EF%BC%8E

30、%E2%80%83%20NAKAI%E2%80%83D%EF%BC%8CMIYAKE%E2%80%83M%EF%BC%8EIntestinal%E2%80%83membrane%E2%80%83function%E2%80%83%0Ain%E2%80%83inflammatory%E2%80%83bowel%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8EPharmaceutics%EF%BC%8C%0A2023%EF%BC%8C16%EF%BC%881%EF%BC%89%EF%BC%9A29%EF%BC%8E

31、MARTINI%E2%80%83E%EF%BC%8CKRUG%E2%80%83S%E2%80%83M%EF%BC%8CSIEGMUND%E2%80%83B%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AMend%E2%80%83your%E2%80%83fences%EF%BC%9AThe%E2%80%83%20epithelial%E2%80%83%20barrier%E2%80%83%20and%E2%80%83its%E2%80%83%0Arelationship%E2%80%83with%E2%80%83mucosal%E2%80%83immunity%E2%80%83in%E2%80%83inflammatory%E2%80%83%0Abowel%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%E2%80%83Mol%E2%80%83Gastroenterol%E2%80%83Hepatol%EF%BC%8C%0A2017%EF%BC%8C4%EF%BC%881%EF%BC%89%EF%BC%9A33-46%EF%BC%8E

32、CHEN%E2%80%83L%EF%BC%8CLUO%E2%80%83S%EF%BC%8CDUPRE%E2%80%83A%EF%BC%8Cet%E2%80%83al%EF%BC%8EThe%E2%80%83%20nuclear%E2%80%83%0Areceptor%E2%80%83HNF4%E2%80%83%20drives%E2%80%83%20a%E2%80%83%20brush%E2%80%83%20border%E2%80%83%20gene%E2%80%83%20program%E2%80%83%0Aconserved%E2%80%83across%E2%80%83murine%E2%80%83intestine%EF%BC%8Ckidney%EF%BC%8Cand%E2%80%83%0Aembryonic%E2%80%83yolk%E2%80%83sac%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Commun%EF%BC%8C2021%EF%BC%8C12%0A%EF%BC%881%EF%BC%89%EF%BC%9A2886%EF%BC%8E

33、MONTENEGRO-MIRANDA%E2%80%83P%E2%80%83S%EF%BC%8Cvan%E2%80%83%20der%E2%80%83%20MEER%E2%80%83%0AJ%E2%80%83H%E2%80%83M%EF%BC%8CJONES%E2%80%83C%EF%BC%8Cet%E2%80%83al%EF%BC%8EA%E2%80%83%20novel%E2%80%83%20organoid%E2%80%83model%E2%80%83%0Aof%E2%80%83damage%E2%80%83and%E2%80%83repair%E2%80%83identifies%E2%80%83HNF4%CE%B1%E2%80%83as%E2%80%83a%E2%80%83critical%E2%80%83%0Aregulator%E2%80%83of%E2%80%83intestinal%E2%80%83epithelial%E2%80%83regeneration%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ACell%E2%80%83Mol%E2%80%83Gastroenterol%E2%80%83Hepatol%EF%BC%8C2020%EF%BC%8C10%EF%BC%882%EF%BC%89%EF%BC%9A%0A209-223%EF%BC%8E

34、ASANO%E2%80%83K%EF%BC%8CMATSUSHITA%E2%80%83T%EF%BC%8CUMENO%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AA%E2%80%83genome-wide%E2%80%83association%E2%80%83study%E2%80%83identifies%E2%80%83three%E2%80%83new%E2%80%83%0Asusceptibility%E2%80%83loci%E2%80%83for%E2%80%83ulcerative%E2%80%83colitis%E2%80%83in%E2%80%83the%E2%80%83Japanese%E2%80%83%0Apopulation%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Genet%EF%BC%8C2009%EF%BC%8C41%EF%BC%8812%EF%BC%89%EF%BC%9A%0A1325-1329%EF%BC%8E

35、%E2%80%83%20SHAO%E2%80%83X%E2%80%83X%EF%BC%8CLIN%E2%80%83D%E2%80%83P%EF%BC%8CSUN%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8EAssociation%E2%80%83%0Aof%E2%80%83%20ulcerative%E2%80%83colitis%E2%80%83with%E2%80%83%20solute-linked%E2%80%83carrier%E2%80%83family%E2%80%83%0A26%E2%80%83member%E2%80%83A3%E2%80%83gene%E2%80%83polymorphisms%E2%80%83and%E2%80%83its%E2%80%83expression%E2%80%83%0Ain%E2%80%83colonic%E2%80%83tissues%E2%80%83in%E2%80%83Chinese%E2%80%83patients%EF%BC%BBJ%EF%BC%BD%EF%BC%8EInt%E2%80%83%20J%E2%80%83%0AColorectal%E2%80%83Dis%EF%BC%8C2018%EF%BC%8C33%EF%BC%889%EF%BC%89%EF%BC%9A1169-1172%EF%BC%8E

36、AMIRI%E2%80%83M%EF%BC%8CJIANG%E2%80%83M%EF%BC%8CSALARI%E2%80%83A%EF%BC%8Cet%E2%80%83al%EF%BC%8EReduced%E2%80%83%0Asurface%E2%80%83%20pH%E2%80%83and%E2%80%83%20upregulated%E2%80%83AE2%E2%80%83anion%E2%80%83exchange%E2%80%83in%E2%80%83%0ASLC26A3-deleted%E2%80%83polarized%E2%80%83intestinal%E2%80%83epithelial%E2%80%83cells%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAm%E2%80%83J%E2%80%83Physiol%E2%80%83Cell%E2%80%83Physiol%EF%BC%8C2024%EF%BC%8C326%0A%EF%BC%883%EF%BC%89%EF%BC%9AC829-C842%EF%BC%8E

37、DING%E2%80%83X%EF%BC%8CLI%E2%80%83D%EF%BC%8CLI%E2%80%83M%EF%BC%8Cet%E2%80%83al%EF%BC%8ESLC26A3%EF%BC%88DRA%EF%BC%89%0Aprevents%E2%80%83TNF-alpha-induced%E2%80%83barrier%E2%80%83dysfunction%E2%80%83and%E2%80%83%0Adextran%E2%80%83sulfate%E2%80%83sodium-induced%E2%80%83acute%E2%80%83colitis%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ALab%E2%80%83Invest%EF%BC%8C2018%EF%BC%8C98%EF%BC%884%EF%BC%89%EF%BC%9A462-476%EF%BC%8E

38、KUMAR%E2%80%83A%EF%BC%8CPRIYAMVADA%E2%80%83S%EF%BC%8CGE%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8EA%E2%80%83%0Anovel%E2%80%83role%E2%80%83of%E2%80%83SLC26A3%E2%80%83in%E2%80%83the%E2%80%83maintenance%E2%80%83of%E2%80%83intestinal%E2%80%83%0Aepithelial%E2%80%83barrier%E2%80%83integrity%EF%BC%BBJ%EF%BC%BD%EF%BC%8EGastroenterology%EF%BC%8C%0A2021%EF%BC%8C160%EF%BC%884%EF%BC%89%EF%BC%9A1240-1255%EF%BC%8Ee3%EF%BC%8E

39、JAYAWARDENA%E2%80%83D%20%EF%BC%8C%20PRIYAMVADA%E2%80%83S%20%EF%BC%8C%0AKAGEYAMA%E2%80%83T%EF%BC%8Cet%E2%80%83al%EF%BC%8ELoss%E2%80%83of%E2%80%83%20SLC26A3%E2%80%83%20results%E2%80%83in%E2%80%83%0Acolonic%E2%80%83mucosal%E2%80%83immune%E2%80%83dysregulation%E2%80%83via%E2%80%83epithelial-immune%E2%80%83cell%E2%80%83crosstalk%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%E2%80%83Mol%E2%80%83Gastroenterol%E2%80%83%0AHepatol%EF%BC%8C2023%EF%BC%8C15%EF%BC%884%EF%BC%89%EF%BC%9A903-919%EF%BC%8E

40、LARABI%E2%80%83A%EF%BC%8CBARNICH%E2%80%83N%EF%BC%8CNGUYEN%E2%80%83H%E2%80%83T%E2%80%83T%EF%BC%8ENew%E2%80%83%0Ainsights%E2%80%83into%E2%80%83the%E2%80%83interplay%E2%80%83between%E2%80%83autophagy%EF%BC%8Cgut%E2%80%83%0Amicrobiota%E2%80%83and%E2%80%83inflammatory%E2%80%83responses%E2%80%83in%E2%80%83IBD%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AAutophagy%EF%BC%8C2020%EF%BC%8C16%EF%BC%881%EF%BC%89%EF%BC%9A38-51%EF%BC%8E

41、GIERY%C5%83SKA%E2%80%83M%EF%BC%8CSZULC-D%C4%84BROWSKA%E2%80%83L%EF%BC%8C%0ASTRUZIK%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8EIntegrity%E2%80%83of%E2%80%83the%E2%80%83intestinal%E2%80%83barrier%EF%BC%9A%0AThe%E2%80%83involvement%E2%80%83of%E2%80%83epithelial%E2%80%83cells%E2%80%83and%E2%80%83microbiota-a%E2%80%83%0Amutual%E2%80%83relationship%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAnimals%EF%BC%8C2022%EF%BC%8C12%0A%EF%BC%882%EF%BC%89%EF%BC%9A145%EF%BC%8E

42、JONES%E2%80%83E%E2%80%83J%EF%BC%8CMATTHEWS%E2%80%83Z%E2%80%83J%EF%BC%8CGUL%E2%80%83L%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AIntegrative%E2%80%83%20analysis%E2%80%83%20of%E2%80%83%20Paneth%E2%80%83%20cell%E2%80%83%20proteomic%E2%80%83%20and%E2%80%83%0Atranscriptomic%E2%80%83%20data%E2%80%83from%E2%80%83intestinal%E2%80%83organoids%E2%80%83%20reveals%E2%80%83%0Afunctional%E2%80%83processes%E2%80%83dependent%E2%80%83on%E2%80%83autophagy%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ADis%E2%80%83Model%E2%80%83Mech%EF%BC%8C2019%EF%BC%8C12%EF%BC%883%EF%BC%89%EF%BC%9Admm037069%EF%BC%8E

43、QUINIOU%E2%80%83G%EF%BC%8CANDROMAQUE%E2%80%83L%EF%BC%8CDUCLAUX%02LORAS%E2%80%83R%EF%BC%8Cet%E2%80%83al%EF%BC%8EImpaired%E2%80%83%20reprogramming%E2%80%83%20of%E2%80%83the%E2%80%83%0Aautophagy%E2%80%83flux%E2%80%83in%E2%80%83maturing%E2%80%83dendritic%E2%80%83cells%E2%80%83from%E2%80%83crohn%E2%80%83%0Adisease%E2%80%83%20patients%E2%80%83%20with%E2%80%83%20core%E2%80%83%20autophagy%E2%80%83%20gene-related%E2%80%83%0Apolymorphisms%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAutophagy%EF%BC%8C2024%EF%BC%8C2%200%0A%EF%BC%888%EF%BC%89%EF%BC%9A1837-1853%EF%BC%8E

44、%E2%80%83%20SERRAMITO-G%C3%93MEZ%E2%80%83I%EF%BC%8CBOADA-ROMERO%E2%80%83E%EF%BC%8C%0AVILLAMUERA%E2%80%83R%EF%BC%8Cet%E2%80%83al%EF%BC%8ERegulation%E2%80%83%20of%E2%80%83%20cytokine%E2%80%83%0Asignaling%E2%80%83through%E2%80%83direct%E2%80%83interaction%E2%80%83between%E2%80%83cytokine%E2%80%83%0Areceptors%E2%80%83and%E2%80%83the%E2%80%83ATG16L1%E2%80%83WD40%E2%80%83domain%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83%0ACommun%EF%BC%8C2020%EF%BC%8C11%EF%BC%881%EF%BC%89%EF%BC%9A5919%EF%BC%8E

45、BOADA-ROMERO%E2%80%83E%EF%BC%8CSERRAMITO-G%C3%93MEZ%E2%80%83I%EF%BC%8C%0ASACRIST%C3%81N%E2%80%83M%E2%80%83P%EF%BC%8Cet%E2%80%83al%EF%BC%8EThe%E2%80%83T300A%E2%80%83Crohn%E2%80%99s%E2%80%83disease%E2%80%83%0Arisk%E2%80%83%20polymorphism%E2%80%83impairs%E2%80%83function%E2%80%83%20of%E2%80%83the%E2%80%83WD40%E2%80%83%0Adomain%E2%80%83of%E2%80%83ATG16L1%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Commun%EF%BC%8C2016%0A%EF%BC%887%EF%BC%89%EF%BC%9A11821%EF%BC%8E

46、SERRAMITO-G%C3%93MEZ%E2%80%83I%EF%BC%8CTERRAZA-SILVESTRE%E2%80%83%0AE%EF%BC%8CFERN%C3%81NDEZ-CABRERA%E2%80%83%C3%81%EF%BC%8Cet%E2%80%83al%EF%BC%8EATG16L1%E2%80%83%0AWD40%E2%80%83domain-dependent%E2%80%83IL10R%EF%BC%88interleukin%E2%80%83%2010%E2%80%83%0Areceptor%EF%BC%89signaling%E2%80%83is%E2%80%83insensitive%E2%80%83to%E2%80%83the%E2%80%83T300A%E2%80%83Crohn%E2%80%83%0Adisease%E2%80%83risk%E2%80%83polymorphism%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAutophagy%EF%BC%8C2022%EF%BC%8C%0A18%EF%BC%8812%EF%BC%89%EF%BC%9A3023-3030%EF%BC%8E

47、NATH%E2%80%83P%EF%BC%8CJENA%E2%80%83K%E2%80%83K%EF%BC%8CMEHTO%E2%80%83S%EF%BC%8Cet%E2%80%83al%EF%BC%8EIRGM%E2%80%83%0Alinks%E2%80%83autoimmunity%E2%80%83to%E2%80%83autophagy%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAutophagy%EF%BC%8C%0A2021%EF%BC%8C17%EF%BC%882%EF%BC%89%EF%BC%9A578-580%EF%BC%8E

48、RAI%E2%80%83P%EF%BC%8CJANARDHAN%E2%80%83K%E2%80%83S%EF%BC%8CMEACHAM%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8EIRGM1%E2%80%83%0Alinks%E2%80%83mitochondrial%E2%80%83quality%E2%80%83control%E2%80%83to%E2%80%83autoimmunity%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Immunol%EF%BC%8C2021%EF%BC%8C22%EF%BC%883%EF%BC%89%EF%BC%9A312-321%EF%BC%8E

49、KAUFMAN%E2%80%83B%E2%80%83A%EF%BC%8CMORA%E2%80%83A%E2%80%83L%EF%BC%8EIRGM1%EF%BC%8Ca%E2%80%83guardian%E2%80%83of%E2%80%83mitochondrial%E2%80%83DAMP-mediated%E2%80%83autoinflammation%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ANat%E2%80%83Immunol%EF%BC%8C2021%EF%BC%8C22%EF%BC%883%EF%BC%89%EF%BC%9A272-273%EF%BC%8E

50、NEWMAN%E2%80%83L%E2%80%83E%EF%BC%8CSHADEL%E2%80%83G%E2%80%83S%EF%BC%8EMitochondrial%E2%80%83DNA%E2%80%83%0Arelease%E2%80%83in%E2%80%83innate%E2%80%83immune%E2%80%83signaling%EF%BC%BBJ%EF%BC%BD%EF%BC%8EAnnu%E2%80%83Rev%E2%80%83%0ABiochem%EF%BC%8C2023%EF%BC%8892%EF%BC%89%EF%BC%9A299-332%EF%BC%8E

51、MEHTO%E2%80%83S%EF%BC%8CJENA%E2%80%83K%E2%80%83K%EF%BC%8CNATH%E2%80%83P%EF%BC%8Cet%E2%80%83al%EF%BC%8EThe%E2%80%83Crohn%E2%80%99s%E2%80%83%0Adisease%E2%80%83%20risk%E2%80%83factor%E2%80%83%20IRGM%E2%80%83limits%E2%80%83NLRP3%E2%80%83inflammasome%E2%80%83%0Aactivation%E2%80%83by%E2%80%83impeding%E2%80%83its%E2%80%83assembly%E2%80%83and%E2%80%83by%E2%80%83mediating%E2%80%83%0Aits%E2%80%83selective%E2%80%83autophagy%EF%BC%BBJ%EF%BC%BD%EF%BC%8EMol%E2%80%83Cell%EF%BC%8C2019%EF%BC%8C73%0A%EF%BC%883%EF%BC%89%EF%BC%9A429-445%EF%BC%8Ee7%EF%BC%8E

52、JENA%E2%80%83K%E2%80%83K%EF%BC%8CMEHTO%E2%80%83S%EF%BC%8CNATH%E2%80%83P%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AAutoimmunity%E2%80%83gene%E2%80%83%20IRGM%E2%80%83%20suppresses%E2%80%83cGAS-STING%E2%80%83%0Aand%E2%80%83%20RIG-I-MAVS%E2%80%83%20signaling%E2%80%83to%E2%80%83%20control%E2%80%83interferon%E2%80%83%0Aresponse%EF%BC%BBJ%EF%BC%BD%EF%BC%8EEMBO%E2%80%83Rep%EF%BC%8C2020%EF%BC%8C21%EF%BC%889%EF%BC%89%EF%BC%9A%0Ae50051%EF%BC%8E

53、TEIMOORI-TOOLABI%E2%80%83L%EF%BC%8CSAMADPOOR%E2%80%83S%EF%BC%8C%0AMEHRTASH%E2%80%83A%EF%BC%8Cet%E2%80%83al%EF%BC%8EAmong%E2%80%83autophagy%E2%80%83genes%EF%BC%8C%0AATG16L1%E2%80%83but%E2%80%83not%E2%80%83IRGM%E2%80%83is%E2%80%83associated%E2%80%83with%E2%80%83Crohn%E2%80%99s%E2%80%83%0Adisease%E2%80%83in%E2%80%83Iranians%EF%BC%8E%EF%BC%BBJ%EF%BC%BD%EF%BC%8EGene%EF%BC%8C2018%EF%BC%88675%EF%BC%89%EF%BC%9A%0A176-184%EF%BC%8E

54、%E2%80%83%20SIMOVIC%E2%80%83I%EF%BC%8CHILMI%E2%80%83I%EF%BC%8CNG%E2%80%83R%E2%80%83T%EF%BC%8Cet%E2%80%83al%EF%BC%8EATG16L1%E2%80%83%0Ars2241880%2FT300A%E2%80%83increases%E2%80%83susceptibility%E2%80%83to%E2%80%83perianal%E2%80%83%0ACrohn%E2%80%99s%E2%80%83disease%EF%BC%9AAn%E2%80%83%20updated%E2%80%83%20meta-analysis%E2%80%83%20on%E2%80%83%0Ainflammatory%E2%80%83bowel%E2%80%83disease%E2%80%83risk%E2%80%83and%E2%80%83clinical%E2%80%83outcomes%EF%BC%8E%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8EUnited%E2%80%83European%E2%80%83Gastroenterol%E2%80%83J%EF%BC%8C2024%EF%BC%8C12%0A%EF%BC%881%EF%BC%89%EF%BC%9A103-121%EF%BC%8E

55、%E2%80%83%20YAMAMOTO%E2%80%83H%EF%BC%8CZHANG%E2%80%83S%EF%BC%8CMIZUSHIMA%E2%80%83N%EF%BC%8E%0AAutophagy%E2%80%83genes%E2%80%83in%E2%80%83biology%E2%80%83and%E2%80%83disease%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83%0ARev%E2%80%83Genet%EF%BC%8C2023%EF%BC%8C24%EF%BC%886%EF%BC%89%EF%BC%9A382-400%EF%BC%8E

56、WITOELAR%E2%80%83A%EF%BC%8CJANSEN%E2%80%83I%E2%80%83E%EF%BC%8CWANG%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AGenome-wide%E2%80%83%20pleiotropy%E2%80%83%20between%E2%80%83%20parkinson%E2%80%83%20disease%E2%80%83%0Aand%E2%80%83autoimmune%E2%80%83diseases%EF%BC%BBJ%EF%BC%BD%EF%BC%8EJAMA%E2%80%83Neurol%EF%BC%8C%0A2017%EF%BC%8C74%EF%BC%887%EF%BC%89%EF%BC%9A780-792%EF%BC%8E

57、%E2%80%83%20KERBER%E2%80%83E%E2%80%83L%EF%BC%8CPADBERG%E2%80%83C%EF%BC%8CKOLL%E2%80%83N%EF%BC%8Cet%E2%80%83al%EF%BC%8EThe%E2%80%83%0Aimportance%E2%80%83of%E2%80%83hypoxia-inducible%E2%80%83factors%EF%BC%88HIF-1%E2%80%83and%E2%80%83%0AHIF-2%EF%BC%89for%E2%80%83the%E2%80%83pathophysiology%E2%80%83of%E2%80%83inflammatory%E2%80%83bowel%E2%80%83%0Adisease%EF%BC%BBJ%EF%BC%BD%EF%BC%8EInt%E2%80%83J%E2%80%83Mol%E2%80%83Sci%EF%BC%8C2020%EF%BC%8C21%EF%BC%8822%EF%BC%89%EF%BC%9A%0A8551%EF%BC%8E

58、%E2%80%83%20CRAMER%E2%80%83T%EF%BC%8CYAMANISHI%E2%80%83Y%EF%BC%8CCLAUSEN%E2%80%83B%E2%80%83E%EF%BC%8Cet%E2%80%83al%EF%BC%8EHIF-1alpha%E2%80%83is%E2%80%83%20essential%E2%80%83for%E2%80%83myeloid%E2%80%83%20cell-mediated%E2%80%83%0Ainflammation%EF%BC%BBJ%EF%BC%BD%EF%BC%8ECell%EF%BC%8C2003%EF%BC%8C112%EF%BC%885%EF%BC%89%EF%BC%9A645-%0A657%EF%BC%8E

59、B%C3%84CKER%E2%80%83V%EF%BC%8CCHEUNG%E2%80%83F%E2%80%83Y%EF%BC%8CSIVEKE%E2%80%83J%E2%80%83T%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AKnockdown%E2%80%83of%E2%80%83myeloid%E2%80%83cell%E2%80%83hypoxia-inducible%E2%80%83factor-%0A1%CE%B1%E2%80%83ameliorates%E2%80%83the%E2%80%83acute%E2%80%83pathology%E2%80%83in%E2%80%83DSS-induced%E2%80%83%0Acolitis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EPLoS%E2%80%83One%EF%BC%8C2017%EF%BC%8C1%202%EF%BC%881%202%EF%BC%89%EF%BC%9A%0Ae0190074%EF%BC%8E

60、%E2%80%83%20FL%C3%9CCK%E2%80%83K%EF%BC%8CBREVES%E2%80%83G%EF%BC%8CFANDREY%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8E%0AHypoxia-inducible%E2%80%83factor%E2%80%831%E2%80%83in%E2%80%83dendritic%E2%80%83cells%E2%80%83is%E2%80%83crucial%E2%80%83%0Afor%E2%80%83the%E2%80%83%20activation%E2%80%83%20of%E2%80%83%20protective%E2%80%83%20regulatory%E2%80%83%20T%E2%80%83%20cells%E2%80%83in%E2%80%83%0Amurine%E2%80%83colitis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EMucosal%E2%80%83Immunol%EF%BC%8C2016%EF%BC%8C9%0A%EF%BC%882%EF%BC%89%EF%BC%9A379-390%EF%BC%8E

61、ASSADI%E2%80%83G%EF%BC%8CSALEH%E2%80%83R%EF%BC%8CHADIZADEH%E2%80%83F%EF%BC%8Cet%E2%80%83al%EF%BC%8ELACC1%E2%80%83%0Apolymorphisms%E2%80%83in%E2%80%83inflammatory%E2%80%83%20bowel%E2%80%83%20disease%E2%80%83%20and%E2%80%83%0Ajuvenile%E2%80%83idiopathic%E2%80%83arthritis%EF%BC%BBJ%EF%BC%BD%EF%BC%8EGenes%E2%80%83Immun%EF%BC%8C%0A2016%EF%BC%8C17%EF%BC%884%EF%BC%89%EF%BC%9A261-264%EF%BC%8E

62、CADER%E2%80%83M%E2%80%83Z%EF%BC%8CBOROVIAK%E2%80%83K%EF%BC%8CZHANG%E2%80%83Q%EF%BC%8Cet%E2%80%83al%EF%BC%8EC13orf31%0A%EF%BC%88FAMIN%EF%BC%89is%E2%80%83a%E2%80%83central%E2%80%83%20regulator%E2%80%83of%E2%80%83immunometabolic%E2%80%83%0Afunction%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Immunol%EF%BC%8C2016%EF%BC%8C17%EF%BC%889%EF%BC%89%EF%BC%9A%0A1046-1056%EF%BC%8E

63、HUANG%E2%80%83C%EF%BC%8CHEDL%E2%80%83M%EF%BC%8CRANJAN%E2%80%83K%EF%BC%8Cet%E2%80%83al%EF%BC%8ELACC1%E2%80%83%0Arequired%E2%80%83for%E2%80%83NOD2-induced%EF%BC%8CER%E2%80%83%20stress-mediated%E2%80%83%0Ainnate%E2%80%83immune%E2%80%83outcomes%E2%80%83in%E2%80%83human%E2%80%83macrophages%E2%80%83and%E2%80%83%0ALACC1%E2%80%83risk%E2%80%83variants%E2%80%83modulate%E2%80%83these%E2%80%83outcomes%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0ACell%E2%80%83Rep%EF%BC%8C2019%EF%BC%8C29%EF%BC%8813%EF%BC%89%EF%BC%9A4525-4539%EF%BC%8Ee4%EF%BC%8E

64、LAHIRI%E2%80%83A%EF%BC%8CHEDL%E2%80%83M%EF%BC%8CYAN%E2%80%83J%EF%BC%8Cet%E2%80%83al%EF%BC%8EHuman%E2%80%83LACC1%E2%80%83%0Aincreases%E2%80%83innate%E2%80%83%20receptor-induced%E2%80%83%20responses%E2%80%83%20and%E2%80%83%20a%E2%80%83%0ALACC1%E2%80%83disease-risk%E2%80%83variant%E2%80%83modulates%E2%80%83these%E2%80%83outcomes%0A%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Commun%EF%BC%8C2017%EF%BC%888%EF%BC%89%EF%BC%9A15614%EF%BC%8E

65、KANG%E2%80%83J%E2%80%83W%EF%BC%8CYAN%E2%80%83J%EF%BC%8CRANJAN%E2%80%83K%EF%BC%8Cet%E2%80%83al%EF%BC%8EMyeloid%E2%80%83%0Acell%E2%80%83%20expression%E2%80%83%20of%E2%80%83%20LACC1%E2%80%83is%E2%80%83%20required%E2%80%83for%E2%80%83%20bacterial%E2%80%83%0Aclearance%E2%80%83and%E2%80%83control%E2%80%83of%E2%80%83intestinal%E2%80%83inflammation%EF%BC%BBJ%EF%BC%BD%EF%BC%8E%0AGastroenterology%EF%BC%8C2020%EF%BC%8C159%EF%BC%883%EF%BC%89%EF%BC%9A1051-1067%EF%BC%8E

66、HUANG%E2%80%83S%E2%80%83C%E2%80%83C%EF%BC%8CEVERTS%E2%80%83B%EF%BC%8CIVANOVA%E2%80%83Y%EF%BC%8Cet%E2%80%83al%EF%BC%8ECell%02intrinsic%E2%80%83lysosomal%E2%80%83lipolysis%E2%80%83is%E2%80%83essential%E2%80%83for%E2%80%83alternative%E2%80%83%0Aactivation%E2%80%83of%E2%80%83macrophages%EF%BC%BBJ%EF%BC%BD%EF%BC%8ENat%E2%80%83Immunol%EF%BC%8C%0A2014%EF%BC%8C15%EF%BC%889%EF%BC%89%EF%BC%9A846-855%EF%BC%8E

1、章汪玥,吴奇泳,赵江林,等.苦荞麸皮对葡聚糖硫酸钠诱导小鼠结肠炎的改善作用[J].食品科学,2025,46(17):180-188.