免疫反应与IBD的发展
Immune Response and the Development of IBD
DOI: 10.12677/jcpm.2025.42284, PDF,   
作者: 贾溟旻, 乔凡瑜, 陈 瑶, 张志云*：云南中医药大学第三附属医院肛肠科，云南 昆明
关键词: IBD；免疫反应；综述；IBD； Immune Response； Overview
摘要: 炎症性肠病(Inflammatory Bowel Disease, IBD)是一种涉及肠道免疫失调、炎性细胞浸润、肠粘膜屏障破坏、肠腔内炎症细胞及细胞因子聚集等复杂病理过程的疾病。近年来在全球范围内发病率显著增加，并造成巨大的疾病负担。免疫反应包括先天性免疫应答及适应性免疫应答，在调节人类健康和疾病中起着至关重要的作用，同样，在IBD的发病过程中，其炎症细胞和细胞因子也发挥了极其重要的调控作用。本文对近年来IBD免疫反应及调控机制方面的研究进展进行综述，以期为IBD的研究及治疗提供新的思路和策略。
Abstract: Inflammatory Bowel Disease (IBD) is a disease involving complex pathological processes such as intestinal immune disorders, inflammatory cell infiltration, intestinal mucosal barrier destruction, intestinal inflammatory cells and cytokine aggregation. In recent years, the incidence rate has increased significantly worldwide and caused a huge burden of disease. Immune response, including congenital immune response and adaptive immune response, plays a vital role in regulating human health and disease. Similarly, in the onset of IBD, its inflammatory cells and cytokines also play an extremely important regulatory role. This article reviews the research progress of IBD immune response and regulatory mechanism in recent years, with a view to providing new ideas and strategies for the research and treatment of IBD.
文章引用：贾溟旻, 乔凡瑜, 陈瑶, 张志云. 免疫反应与IBD的发展[J]. 临床个性化医学, 2025, 4(2): 1122-1131. https://doi.org/10.12677/jcpm.2025.42284

参考文献

[1] Kaplan, G.G. (2015) The Global Burden of IBD: From 2015 to 2025. Nature Reviews Gastroenterology & Hepatology, 12, 720-727. [Google Scholar] [CrossRef] [PubMed]
[2] Ng, S.C., Shi, H.Y., Hamidi, N., Underwood, F.E., Tang, W., Benchimol, E.I., et al. (2017) The Worldwide Incidence and Prevalence of Inflammatory Bowel Disease in the 21st Century: A Systematic Review of Population-Based Studies: Digestive Disease Week. Gastroenterology, 152, S970-S971. [Google Scholar] [CrossRef] 
[3] Jones, G., Lyons, M., Plevris, N., Jenkinson, P.W., Bisset, C., Burgess, C., et al. (2019) IBD Prevalence in Lothian, Scotland, Derived by Capture-Recapture Methodology. Gut, 68, 1953-1960. [Google Scholar] [CrossRef] [PubMed]
[4] Zhang, H., Zhang, M., Chen, X., Guo, M., Zhou, R., Lv, H., et al. (2022) Risk of Malignancy in Patients with Inflammatory Bowel Disease: A Population‐Based Cohort Study from China. International Journal of Cancer, 150, 1770-1778. [Google Scholar] [CrossRef] [PubMed]
[5] Guan, Q. (2019) A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. Journal of Immunology Research, 2019, Article ID: 7247238. [Google Scholar] [CrossRef] [PubMed]
[6] Pandian, N. and Kanneganti, T. (2022) Panoptosis: A Unique Innate Immune Inflammatory Cell Death Modality. The Journal of Immunology, 209, 1625-1633. [Google Scholar] [CrossRef] [PubMed]
[7] Zhou, G., Yu, L., Fang, L., Yang, W., Yu, T., Miao, Y., et al. (2017) CD177+ Neutrophils as Functionally Activated Neutrophils Negatively Regulate IBD. Gut, 67, 1052-1063. [Google Scholar] [CrossRef] [PubMed]
[8] Friedrich, M., Pohin, M., Jackson, M.A., Korsunsky, I., Bullers, S.J., Rue-Albrecht, K., et al. (2021) Il-1-Driven Stromal-Neutrophil Interactions Define a Subset of Patients with Inflammatory Bowel Disease That Does Not Respond to Therapies. Nature Medicine, 27, 1970-1981. [Google Scholar] [CrossRef] [PubMed]
[9] Camilleri, M., Madsen, K., Spiller, R., Van Meerveld, B.G. and Verne, G.N. (2012) Intestinal Barrier Function in Health and Gastrointestinal Disease. Neurogastroenterology & Motility, 24, 503-512. [Google Scholar] [CrossRef] [PubMed]
[10] Foerster, E.G., Mukherjee, T., Cabral-Fernandes, L., Rocha, J.D.B., Girardin, S.E. and Philpott, D.J. (2021) How Autophagy Controls the Intestinal Epithelial Barrier. Autophagy, 18, 86-103. [Google Scholar] [CrossRef] [PubMed]
[11] Wardle, E. (2010) Th-17 Lymphocytes. Saudi Journal of Kidney Diseases and Transplantation: An Official Publication of the Saudi Center for Organ Transplantation, Saudi Arabia, 21, 954-956.
[12] Nissilä, E., Korpela, K., Lokki, A.I., Paakkanen, R., Jokiranta, S., de Vos, W.M., et al. (2017) C4B Gene Influences Intestinal Microbiota through Complement Activation in Patients with Paediatric-Onset Inflammatory Bowel Disease. Clinical and Experimental Immunology, 190, 394-405. [Google Scholar] [CrossRef] [PubMed]
[13] Steinbach, E.C. and Plevy, S.E. (2014) The Role of Macrophages and Dendritic Cells in the Initiation of Inflammation in IBD. Inflammatory Bowel Diseases, 20, 166-175. [Google Scholar] [CrossRef] [PubMed]
[14] Mateer, S.W., Mathe, A., Bruce, J., Liu, G., Maltby, S., Fricker, M., et al. (2018) IL-6 Drives Neutrophil-Mediated Pulmonary Inflammation Associated with Bacteremia in Murine Models of Colitis. The American Journal of Pathology, 188, 1625-1639. [Google Scholar] [CrossRef] [PubMed]
[15] Stark, M.A., Huo, Y., Burcin, T.L., Morris, M.A., Olson, T.S. and Ley, K. (2005) Phagocytosis of Apoptotic Neutrophils Regulates Granulopoiesis via IL-23 and IL-17. Immunity, 22, 285-294. [Google Scholar] [CrossRef] [PubMed]
[16] dos Santos Ramos, A., Viana, G.C.S., de Macedo Brigido, M. and Almeida, J.F. (2021) Neutrophil Extracellular Traps in Inflammatory Bowel Diseases: Implications in Pathogenesis and Therapeutic Targets. Pharmacological Research, 171, Article ID: 105779. [Google Scholar] [CrossRef] [PubMed]
[17] Fan, F.Y., Sang, L.X., et al. (2017) Catechins and Their Therapeutic Benefits to Inflammatory Bowel Disease. Molecules, 22, Article 484.
[18] Yao, H. and Tang, G. (2022) Macrophages in Intestinal Fibrosis and Regression. Cellular Immunology, 381, Article ID: 104614. [Google Scholar] [CrossRef] [PubMed]
[19] Spalinger, M.R., Sayoc-Becerra, A., Ordookhanian, C., Canale, V., Santos, A.N., King, S.J., et al. (2020) The JAK Inhibitor Tofacitinib Rescues Intestinal Barrier Defects Caused by Disrupted Epithelial-Macrophage Interactions. Journal of Crohn’s and Colitis, 15, 471-484. [Google Scholar] [CrossRef] [PubMed]
[20] Liu, X., Zhou, M., Dai, Z., Luo, S., Shi, Y., He, Z., et al. (2022) Salidroside Alleviates Ulcerative Colitis via Inhibiting Macrophage Pyroptosis and Repairing the Dysbacteriosis‐Associated Th17/Treg Imbalance. Phytotherapy Research, 37, 367-382. [Google Scholar] [CrossRef] [PubMed]
[21] Kalischuk, L.D. and Buret, A.G. (2010) A Role for Campylobacter Jejuni-Induced Enteritis in Inflammatory Bowel Disease? American Journal of Physiology-Gastrointestinal and Liver Physiology, 298, G1-G9. [Google Scholar] [CrossRef] [PubMed]
[22] Wolfgang, H., Bruce, E.S., Steve, L., et al. (2012) Secukinumab, a Human Anti-IL-17A Monoclonal Antibody, for Moderate to Severe Crohn’s Disease: Unexpected Results of a Randomised, Double-Blind Placebo-Controlled Trial. Gut, 61, 1693-1700.
[23] Ananthakrishnan, A.N., Bernstein, C.N., Iliopoulos, D., Macpherson, A., Neurath, M.F., Ali, R.A.R., et al. (2017) Environmental Triggers in IBD: A Review of Progress and Evidence. Nature Reviews Gastroenterology & Hepatology, 15, 39-49. [Google Scholar] [CrossRef] [PubMed]
[24] Faleiro, R., Liu, J., Karunarathne, D., Edmundson, A., Winterford, C., Nguyen, T.H., et al. (2019) Crohn’s Disease Is Facilitated by a Disturbance of Programmed Death‐1 Ligand 2 on Blood Dendritic Cells. Clinical & Translational Immunology, 8, e1071. [Google Scholar] [CrossRef] [PubMed]
[25] Xavier, R.J. and Podolsky, D.K. (2007) Unravelling the Pathogenesis of Inflammatory Bowel Disease. Nature, 448, 427-434. [Google Scholar] [CrossRef] [PubMed]
[26] Efferth, T. and Oesch, F. (2021) The Immunosuppressive Activity of Artemisinin‐Type Drugs Towards Inflammatory and Autoimmune Diseases. Medicinal Research Reviews, 41, 3023-3061. [Google Scholar] [CrossRef] [PubMed]
[27] Yuan, S., Wang, M., Han, J., Feng, C., Wang, M., Wang, M., et al. (2023) Improved Colonic Inflammation by Nervonic Acid via Inhibition of NF-κB Signaling Pathway of DSS-Induced Colitis Mice. Phytomedicine, 112, Article ID: 154702. [Google Scholar] [CrossRef] [PubMed]
[28] Shimizu, M. (2017) Multifunctions of Dietary Polyphenols in the Regulation of Intestinal Inflammation. Journal of Food and Drug Analysis, 25, 93-99. [Google Scholar] [CrossRef] [PubMed]
[29] Li, Z., Yu, E., Wang, G., Yu, D., Zhang, K., Gong, W., et al. (2018) Broad Bean (Vicia faba L.) Induces Intestinal Inflammation in Grass Carp (Ctenopharyngodon idellus C. et V) by Increasing Relative Abundances of Intestinal Gram-Negative and Flagellated Bacteria. Frontiers in Microbiology, 9, Article 1913. [Google Scholar] [CrossRef] [PubMed]
[30] Wei, W., Mu, S., Han, Y., Chen, Y., Kuang, Z., Wu, X., et al. (2022) Gpr174 Knockout Alleviates DSS-Induced Colitis via Regulating the Immune Function of Dendritic Cells. Frontiers in Immunology, 13, Article 841254. [Google Scholar] [CrossRef] [PubMed]
[31] Yao, X., Huang, J., Zhong, H., Shen, N., Faggioni, R., Fung, M., et al. (2014) Targeting Interleukin-6 in Inflammatory Autoimmune Diseases and Cancers. Pharmacology & Therapeutics, 141, 125-139. [Google Scholar] [CrossRef] [PubMed]
[32] Li, X., Ling, Y., Huang, X., Zhou, T., Wu, S., Zhang, S., et al. (2023) Rosa roxburghii Tratt Fruit Extract Prevents DSS-Induced Ulcerative Colitis in Mice by Modulating the Gut Microbiota and the IL-17 Signaling Pathway. Nutrients, 15, Article 4560. [Google Scholar] [CrossRef] [PubMed]
[33] Segers, A. and de Vos, W.M. (2023) Mode of Action of Akkermansia muciniphila in the Intestinal Dialogue: Role of Extracellular Proteins, Metabolites and Cell Envelope Components. Microbiome Research Reports, 2, Article 6. [Google Scholar] [CrossRef] [PubMed]
[34] Hershberg, R.M. (2002) V. Polarized Compartmentalization of Antigen Processing and Toll-Like Receptor Signaling in Intestinal Epithelial Cells. American Journal of Physiology-Gastrointestinal and Liver Physiology, 283, G833-G839. [Google Scholar] [CrossRef] [PubMed]
[35] Heller, F., Florian, P., Bojarski, C., Richter, J., Christ, M., Hillenbrand, B., et al. (2005) Interleukin-13 Is the Key Effector Th2 Cytokine in Ulcerative Colitis That Affects Epithelial Tight Junctions, Apoptosis, and Cell Restitution. Gastroenterology, 129, 550-564. [Google Scholar] [CrossRef] [PubMed]
[36] Danese, S. (2011) Immune and Nonimmune Components Orchestrate the Pathogenesis of Inflammatory Bowel Disease. American Journal of Physiology-Gastrointestinal and Liver Physiology, 300, G716-G722. [Google Scholar] [CrossRef] [PubMed]
[37] Ricciardelli, I., Lindley, K.J., Londei, M. and Quaratino, S. (2008) Anti Tumour Necrosis‐α Therapy Increases the Number of FOXP3+ Regulatory T Cells in Children Affected by Crohn’s Disease. Immunology, 125, 178-183. [Google Scholar] [CrossRef] [PubMed]
[38] Ala, M. (2021) Tryptophan Metabolites Modulate Inflammatory Bowel Disease and Colorectal Cancer by Affecting Immune System. International Reviews of Immunology, 41, 326-345. [Google Scholar] [CrossRef] [PubMed]
[39] Wu, J., Wei, Z., Cheng, P., Qian, C., Xu, F., Yang, Y., et al. (2020) Rhein Modulates Host Purine Metabolism in Intestine through Gut Microbiota and Ameliorates Experimental Colitis. Theranostics, 10, 10665-10679. [Google Scholar] [CrossRef] [PubMed]
[40] Fu, Y., Ni, J., Chen, J., Ma, G., Zhao, M., Zhu, S., et al. (2020) Dual-Functionalized MSCs That Express CX3CR1 and IL-25 Exhibit Enhanced Therapeutic Effects on Inflammatory Bowel Disease. Molecular Therapy, 28, 1214-1228. [Google Scholar] [CrossRef] [PubMed]
[41] Liu, Y., Tang, B., Wang, F., Tang, L., Lei, Y., Luo, Y., et al. (2020) Parthenolide Ameliorates Colon Inflammation through Regulating Treg/Th17 Balance in a Gut Microbiota-Dependent Manner. Theranostics, 10, 5225-5241. [Google Scholar] [CrossRef] [PubMed]
[42] Xia, X., Zhang, Y., Zhu, L., Ying, Y., Hao, W., Wang, L., et al. (2023) Liquiritin Apioside Alleviates Colonic Inflammation and Accompanying Depression-Like Symptoms in Colitis by Gut Metabolites and the Balance of Th17/Treg. Phytomedicine, 120, Article ID: 155039. [Google Scholar] [CrossRef] [PubMed]
[43] 徐小芳, 吕小平. PTGER4基因与炎症性肠病关系的研究进展[J]. 山东医药, 2019, 59(8): 100-103.
[44] Yu, L., Zhou, B., Zhu, Y., Li, L., Zhong, Y., Zhu, L., et al. (2023) HSF1 Promotes CD69+ Treg Differentiation to Inhibit Colitis Progression. Theranostics, 13, 1892-1905. [Google Scholar] [CrossRef] [PubMed]