自噬在炎症性肠病免疫稳态的研究进展
Research Progress of Autophagy in Immune Homeostasis in Inflammatory Bowel Disease
DOI: 10.12677/acm.2025.153631, PDF,   
作者: 彭冰霞, 王晓娟：赣南医科大学第一临床医学院，江西 赣州；袁 建*：广东省人民医院赣州医院消化内科，江西 赣州
关键词: 自噬；免疫稳态；炎症性肠病；克罗恩病；溃疡性结肠炎；Autophagy； Immune Homeostasis； Inflammatory Bowel Disease； Crohn’s Disease； Ulcerative Colitis
摘要: 近年来，越来越多的研究表明，自噬在调节免疫反应和炎症中发挥着重要作用。肠道作为机体重要的免疫器官，其内部的免疫细胞在自噬过程中可能对肠道炎症的发生与发展产生深远的影响。随着自噬在IBD的研究深入，发现肠道免疫细胞的异常自噬，可显著削弱肠道的免疫平衡和黏膜屏障的完整性，后者是IBD出现病情进展的重要环节。本文将系统地回顾自噬与肠道炎症及肠道免疫细胞之间的相互关系，以期为相关疾病的防治提供新的思路和方向。
Abstract: In recent years, more and more studies have shown that autophagy plays an important role in regulating immune response and inflammation. Intestinal tract is an important immune organ of the body, and its internal immune cells may have a profound impact on the occurrence and development of intestinal inflammation in the process of autophagy. With the in-depth study of autophagy in IBD, it has been found that abnormal autophagy of intestinal immune cells can significantly weaken the immune balance of the intestine and the integrity of the mucosal barrier, which is an important part of the progression of IBD. This article will systematically review the relationship between autophagy, intestinal inflammation and intestinal immune cells, in order to provide new ideas and directions for the prevention and treatment of related diseases.
文章引用：彭冰霞, 王晓娟, 袁建. 自噬在炎症性肠病免疫稳态的研究进展[J]. 临床医学进展, 2025, 15(3): 415-421. https://doi.org/10.12677/acm.2025.153631

参考文献

[1] Hampe, J., Franke, A., Rosenstiel, P., Till, A., Teuber, M., Huse, K., et al. (2006) A Genome-Wide Association Scan of Nonsynonymous SNPs Identifies a Susceptibility Variant for Crohn Disease in ATG16L1. Nature Genetics, 39, 207-211. [Google Scholar] [CrossRef] [PubMed]
[2] Levine, B., Mizushima, N. and Virgin, H.W. (2011) Autophagy in Immunity and Inflammation. Nature, 469, 323-335. [Google Scholar] [CrossRef] [PubMed]
[3] Faas, M.M. and de Vos, P. (2020) Mitochondrial Function in Immune Cells in Health and Disease. Biochimica et Biophysica Acta (BBA)—Molecular Basis of Disease, 1866, Article ID: 165845. [Google Scholar] [CrossRef] [PubMed]
[4] Mizushima, N., Yoshimori, T. and Ohsumi, Y. (2011) The Role of ATG Proteins in Autophagosome Formation. Annual Review of Cell and Developmental Biology, 27, 107-132. [Google Scholar] [CrossRef] [PubMed]
[5] Saxton, R.A. and Sabatini, D.M. (2017) mTOR Signaling in Growth, Metabolism, and Disease. Cell, 169, 361-371. [Google Scholar] [CrossRef] [PubMed]
[6] Blommaart, E.F.C., Luiken, J.J.F.P., Blommaart, P.J.E., van Woerkom, G.M. and Meijer, A.J. (1995) Phosphorylation of Ribosomal Protein S6 Is Inhibitory for Autophagy in Isolated Rat Hepatocytes. Journal of Biological Chemistry, 270, 2320-2326. [Google Scholar] [CrossRef] [PubMed]
[7] Lin, S. and Hardie, D.G. (2018) AMPK: Sensing Glucose as Well as Cellular Energy Status. Cell Metabolism, 27, 299-313. [Google Scholar] [CrossRef] [PubMed]
[8] Poillet-Perez, L., Sharp, D.W., Yang, Y., Laddha, S.V., Ibrahim, M., Bommareddy, P.K., et al. (2020) Autophagy Promotes Growth of Tumors with High Mutational Burden by Inhibiting a T-Cell Immune Response. Nature Cancer, 1, 923-934. [Google Scholar] [CrossRef] [PubMed]
[9] Thein, W., Po, W.W., Choi, W.S. and Sohn, U.D. (2021) Autophagy and Digestive Disorders: Advances in Understanding and Therapeutic Approaches. Biomolecules & Therapeutics, 29, 353-364. [Google Scholar] [CrossRef] [PubMed]
[10] Hu, C., Liao, S., Lv, L., Li, C. and Mei, Z. (2023) Intestinal Immune Imbalance Is an Alarm in the Development of IBD. Mediators of Inflammation, 2023, Article ID: 1073984. [Google Scholar] [CrossRef] [PubMed]
[11] Chiok, K. and Bose, S. (2022) A Novel Viral Regulatory Network for Autophagy Induction: Respiratory Syncytial Virus NS2 Protein Regulates Autophagy by Modulating BECN1 Isgylation and Protein Stability. Autophagy Reports, 1, 219-222. [Google Scholar] [CrossRef] [PubMed]
[12] He, W., Xiong, W. and Xia, X. (2019) Autophagy Regulation of Mammalian Immune Cells. In: Cui, J., Ed., Autophagy Regulation of Innate Immunity, Springer, 7-22. [Google Scholar] [CrossRef] [PubMed]
[13] Starr, T.K., Jameson, S.C. and Hogquist, K.A. (2003) Positive and Negative Selection of T Cells. Annual Review of Immunology, 21, 139-176. [Google Scholar] [CrossRef] [PubMed]
[14] Schmid, D., Pypaert, M. and Münz, C. (2007) Antigen-loading Compartments for Major Histocompatibility Complex Class II Molecules Continuously Receive Input from Autophagosomes. Immunity, 26, 79-92. [Google Scholar] [CrossRef] [PubMed]
[15] Kovacs, J.R., Li, C., Yang, Q., Li, G., Garcia, I.G., Ju, S., et al. (2011) Autophagy Promotes T-Cell Survival through Degradation of Proteins of the Cell Death Machinery. Cell Death & Differentiation, 19, 144-152. [Google Scholar] [CrossRef] [PubMed]
[16] Rivera Vargas, T., Cai, Z., Shen, Y., Dosset, M., Benoit-Lizon, I., Martin, T., et al. (2017) Selective Degradation of PU.1 during Autophagy Represses the Differentiation and Antitumour Activity of TH9 Cells. Nature Communications, 8, Article No. 559. [Google Scholar] [CrossRef] [PubMed]
[17] Lin, R., Ma, C., Fang, L., Xu, C., Zhang, C., Wu, X., et al. (2022) TOB1 Blocks Intestinal Mucosal Inflammation through Inducing ID2-Mediated Suppression of Th1/Th17 Cell Immune Responses in IBD. Cellular and Molecular Gastroenterology and Hepatology, 13, 1201-1221. [Google Scholar] [CrossRef] [PubMed]
[18] Kabat, A.M., Harrison, O.J., Riffelmacher, T., Moghaddam, A.E., Pearson, C.F., Laing, A., et al. (2016) The Autophagy Gene Atg16l1 Differentially Regulates Treg and TH2 Cells to Control Intestinal Inflammation. eLife, 5, e12444. [Google Scholar] [CrossRef] [PubMed]
[19] Michalek, R.D., Gerriets, V.A., Jacobs, S.R., Macintyre, A.N., MacIver, N.J., Mason, E.F., et al. (2011) Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets. The Journal of Immunology, 186, 3299-3303. [Google Scholar] [CrossRef] [PubMed]
[20] Wei, J., Long, L., Yang, K., Guy, C., Shrestha, S., Chen, Z., et al. (2016) Autophagy Enforces Functional Integrity of Regulatory T Cells by Coupling Environmental Cues and Metabolic Homeostasis. Nature Immunology, 17, 277-285. [Google Scholar] [CrossRef] [PubMed]
[21] Puleston, D.J., Zhang, H., Powell, T.J., Lipina, E., Sims, S., Panse, I., et al. (2014) Autophagy Is a Critical Regulator of Memory CD8+ T Cell Formation. eLife, 3, e03706. [Google Scholar] [CrossRef] [PubMed]
[22] Murera, D., Arbogast, F., Arnold, J., Bouis, D., Muller, S. and Gros, F. (2018) CD4 T Cell Autophagy Is Integral to Memory Maintenance. Scientific Reports, 8, Article No. 5951. [Google Scholar] [CrossRef] [PubMed]
[23] Ziegler, P.K., Bollrath, J., Pallangyo, C.K., Matsutani, T., Canli, Ö., De Oliveira, T., et al. (2018) Mitophagy in Intestinal Epithelial Cells Triggers Adaptive Immunity during Tumorigenesis. Cell, 174, 88-101.e16. [Google Scholar] [CrossRef] [PubMed]
[24] Franco, F., Bevilacqua, A., Wu, R., Kao, K., Lin, C., Rousseau, L., et al. (2023) Regulatory Circuits of Mitophagy Restrict Distinct Modes of Cell Death during Memory CD8(+) T Cell Formation. Science Immunology, 8, eadf7579. [Google Scholar] [CrossRef] [PubMed]
[25] Chen, H., Wu, X., Xu, C., Lin, J. and Liu, Z. (2021) Dichotomous Roles of Neutrophils in Modulating Pathogenic and Repair Processes of Inflammatory Bowel Diseases. Precision Clinical Medicine, 4, 246-257. [Google Scholar] [CrossRef] [PubMed]
[26] Riffelmacher, T., Clarke, A., Richter, F.C., Stranks, A., Pandey, S., Danielli, S., et al. (2017) Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation. Immunity, 47, 466-480.e5. [Google Scholar] [CrossRef] [PubMed]
[27] Leveque-El Mouttie, L., Vu, T., Lineburg, K.E., Kuns, R.D., Bagger, F.O., Teal, B.E., et al. (2015) Autophagy Is Required for Stem Cell Mobilization by G-CSF. Blood, 125, 2933-2936. [Google Scholar] [CrossRef] [PubMed]
[28] Rožman, S., Yousefi, S., Oberson, K., Kaufmann, T., Benarafa, C. and Simon, H.U. (2014) The Generation of Neutrophils in the Bone Marrow Is Controlled by Autophagy. Cell Death & Differentiation, 22, 445-456. [Google Scholar] [CrossRef] [PubMed]
[29] Zhang, Y., Morgan, M.J., Chen, K., Choksi, S. and Liu, Z. (2012) Induction of Autophagy Is Essential for Monocyte-Macrophage Differentiation. Blood, 119, 2895-2905. [Google Scholar] [CrossRef] [PubMed]
[30] Qing, J., Zhang, Z., Novák, P., Zhao, G. and Yin, K. (2020) Mitochondrial Metabolism in Regulating Macrophage Polarization: An Emerging Regulator of Metabolic Inflammatory Diseases. Acta Biochimica et Biophysica Sinica, 52, 917-926. [Google Scholar] [CrossRef] [PubMed]
[31] Zareie, M., Singh, P.K., Irvine, E.J., Sherman, P.M., McKay, D.M. and Perdue, M.H. (2001) Monocyte/Macrophage Activation by Normal Bacteria and Bacterial Products: Implications for Altered Epithelial Function in Crohn’s Disease. The American Journal of Pathology, 158, 1101-1109. [Google Scholar] [CrossRef] [PubMed]
[32] Smythies, L.E., Sellers, M., Clements, R.H., Mosteller-Barnum, M., Meng, G., Benjamin, W.H., et al. (2005) Human Intestinal Macrophages Display Profound Inflammatory Anergy Despite Avid Phagocytic and Bacteriocidal Activity. Journal of Clinical Investigation, 115, 66-75. [Google Scholar] [CrossRef] [PubMed]
[33] Seyedizade, S.S., Afshari, K., Bayat, S., Rahmani, F., Momtaz, S., Rezaei, N., et al. (2020) Current Status of M1 and M2 Macrophages Pathway as Drug Targets for Inflammatory Bowel Disease. Archivum Immunologiae et Therapiae Experimentalis, 68, Article No. 10. [Google Scholar] [CrossRef] [PubMed]
[34] Jacquel, A., Obba, S., Boyer, L., Dufies, M., Robert, G., Gounon, P., et al. (2012) Autophagy Is Required for Csf-1-Induced Macrophagic Differentiation and Acquisition of Phagocytic Functions. Blood, 119, 4527-4531. [Google Scholar] [CrossRef] [PubMed]
[35] Huang, S.C., Everts, B., Ivanova, Y., O’Sullivan, D., Nascimento, M., Smith, A.M., et al. (2014) Cell-Intrinsic Lysosomal Lipolysis Is Essential for Alternative Activation of Macrophages. Nature Immunology, 15, 846-855. [Google Scholar] [CrossRef] [PubMed]
[36] Liu, X., Wang, Y., Shao, P., Chen, Y., Yang, C., Wang, J., et al. (2024) Sargentodoxa Cuneata and Patrinia Villosa Extract Inhibits LPS-Induced Inflammation by Shifting Macrophages Polarization through FAK/PI3K/Akt Pathway Regulation and Glucose Metabolism Reprogramming. Journal of Ethnopharmacology, 318, Article ID: 116855. [Google Scholar] [CrossRef] [PubMed]
[37] Liu, T., Wang, L., Liang, P., Wang, X., Liu, Y., Cai, J., et al. (2020) USP19 Suppresses Inflammation and Promotes M2-Like Macrophage Polarization by Manipulating NLRP3 Function via Autophagy. Cellular & Molecular Immunology, 18, 2431-2442. [Google Scholar] [CrossRef] [PubMed]
[38] Stranks, A.J., Hansen, A.L., Panse, I., Mortensen, M., Ferguson, D.J.P., Puleston, D.J., et al. (2015) Autophagy Controls Acquisition of Aging Features in Macrophages. Journal of Innate Immunity, 7, 375-391. [Google Scholar] [CrossRef] [PubMed]
[39] Hubbard-Lucey, V.M., Shono, Y., Maurer, K., West, M.L., Singer, N.V., Ziegler, C.G.K., et al. (2014) Autophagy Gene Atg16l1 Prevents Lethal T Cell Alloreactivity Mediated by Dendritic Cells. Immunity, 41, 579-591. [Google Scholar] [CrossRef] [PubMed]
[40] Cooney, R., Baker, J., Brain, O., Danis, B., Pichulik, T., Allan, P., et al. (2009) NOD2 Stimulation Induces Autophagy in Dendritic Cells Influencing Bacterial Handling and Antigen Presentation. Nature Medicine, 16, 90-97. [Google Scholar] [CrossRef] [PubMed]
[41] Weindel, C.G., Richey, L.J., Mehta, A.J., Shah, M. and Huber, B.T. (2017) Autophagy in Dendritic Cells and B Cells Is Critical for the Inflammatory State of Tlr7-Mediated Autoimmunity. The Journal of Immunology, 198, 1081-1092. [Google Scholar] [CrossRef] [PubMed]

为你推荐