IL-22在肝纤维化发生发展中的作用

孟昱希; 霍丽娟

doi:10.3969/j.issn.1001-5256.2021.12.039

IL-22在肝纤维化发生发展中的作用

DOI: 10.3969/j.issn.1001-5256.2021.12.039

孟昱希¹,
霍丽娟^2, ,

1.
山西医科大学第二医院消化内科，太原 030001
2.
山西医科大学第一医院消化内科，太原 030001

详细信息

通信作者:
霍丽娟，mymail5296@163.com

中图分类号: R575.2
计量
- 文章访问数: 691
- HTML全文浏览量: 98
- PDF下载量: 55
- 被引次数: 0
出版历程
- 收稿日期: 2021-04-22
- 录用日期: 2021-06-07
- 出版日期: 2021-12-20

Role of interleukin-22 in the development and progression of liver fibrosis

Yuxi MENG¹,
Lijuan HUO^{2
, ,}

1.
Department of Gastroenterology, The Second Hospital Affiliated to Shanxi Medical University, Taiyuan 030001, China
2.
Department of Gastroenterology, The First Hospital Affiliated to Shanxi Medical University, Taiyuan 030001, China

摘要

摘要: 肝纤维化是慢性肝损伤过程中持续的炎症反应和慢性瘢痕愈合反应的结果。肝纤维化进展可导致肝硬化、门静脉高压和肝衰竭，最终只能进行肝移植。IL-22属于IL-10家族，是目前发现的唯一由免疫细胞产生但不作用于免疫细胞的细胞因子，可通过与其受体IL-22R1/IL-10R2结合而发挥作用，近年来在肝病研究领域中备受关注。IL-22在肝脏疾病中既有抗炎、促进肝再生和组织修复的作用，又有促炎作用。在某些致病条件下，IL-22通过减少纤维化发挥保护肝脏的作用，然而其与肝纤维化的关系目前仍存在争议。对于不同病因引起的肝纤维化，其作用及相关机制也不相同。现就IL-22在病毒感染(HBV、HCV)、酒精、高脂和自身免疫等原因所致肝纤维化中的作用及可能的机制进行综述。
- 肝硬化 /
- 白细胞介素22 /
- 病理过程
Abstract: Liver fibrosis is the result of persistent inflammatory response and chronic scar healing response during chronic liver injury and may progress to liver cirrhosis, portal hypertension, and liver failure, which finally requires liver transplantation. Interleukin-22 (IL-22) belongs to the IL-10 family and is the only cytokine that is produced by immune cells but does not act on immune cells. IL-22 plays a role by binding to its receptors IL-22R1 and IL-10R2, which has attracted much attention in the field of liver disease research in recent years. IL-22 not only plays the role of anti-inflammation and promotion of liver regeneration and tissue repair, but also has a pro-inflammatory effect in liver diseases, and it exerts a protective effect on the liver by reducing fibrosis in some pathological conditions, but there are still controversies over its association with liver fibrosis. IL-22 has different effects and mechanisms in liver fibrosis caused by different etiologies. This article reviews the role and possible mechanisms of IL-22 in liver fibrosis caused by viral infection (HBV and HCV), alcohol, high-fat diet, and autoimmunity.
- Liver Cirrhosis /
- Interleukin-22 /
- Pathologic Processes

HTML全文

参考文献(32)

[1]	BÖTTCHER K, PINZANI M. Pathophysiology of liver fibrosis and the methodological barriers to the development of anti-fibrogenic agents[J]. Adv Drug Deliv Rev, 2017, 121: 3-8. DOI: 10.1016/j.addr.2017.05.016.
[2]	DUVAL F, MORENO-CUEVAS JE, GONZÁLEZ-GARZA MT, et al. Liver fibrosis and protection mechanisms action of medicinal plants targeting apoptosis of hepatocytes and hepatic stellate cells[J]. Adv Pharmacol Sci, 2014, 2014: 373295. DOI: 10.1155/2014/373295.
[3]	LEE YA, WALLACE MC, FRIEDMAN SL. Pathobiology of liver fibrosis: A translational success story[J]. Gut, 2015, 64(5): 830-841. DOI: 10.1136/gutjnl-2014-306842.
[4]	DUMOUTIER L, LOUAHED J, RENAULD JC. Cloning and characterization of IL-10-related T cell-derived inducible factor (IL-TIF), a novel cytokine structurally related to IL-10 and inducible by IL-9[J]. J Immunol, 2000, 164(4): 1814-1819. DOI: 10.4049/jimmunol.164.4.1814.
[5]	DUDAKOV JA, HANASH AM, van DEN BRINK MR. Interleukin-22: Immunobiology and pathology[J]. Annu Rev Immunol, 2015, 33: 747-785. DOI: 10.1146/annurev-immunol-032414-112123.
[6]	SABAT R, OUYANG W, WOLK K. Therapeutic opportunities of the IL-22-IL-22R1 system[J]. Nat Rev Drug Discov, 2014, 13(1): 21-38. DOI: 10.1038/nrd4176.
[7]	GAO B, XIANG X. Interleukin-22 from bench to bedside: A promising drug for epithelial repair[J]. Cell Mol Immunol, 2019, 16(7): 666-667. DOI: 10.1038/s41423-018-0055-6.
[8]	WOLK K, WITTE E, WITTE K, et al. Biology of interleukin-22[J]. Semin Immunopathol, 2010, 32(1): 17-31. DOI: 10.1007/s00281-009-0188-x.
[9]	PARK O, WANG H, WENG H, et al. In vivo consequences of liver-specific interleukin-22 expression in mice: Implications for human liver disease progression[J]. Hepatology, 2011, 54(1): 252-261. DOI: 10.1002/hep.24339.
[10]	XIANG X, GUI H, KING NJ, et al. IL-22 and non-ELR-CXC chemokine expression in chronic hepatitis B virus-infected liver[J]. Immunol Cell Biol, 2012, 90(6): 611-619. DOI: 10.1038/icb.2011.79.
[11]	FENG D, KONG X, WENG H, et al. Interleukin-22 promotes proliferation of liver stem/progenitor cells in mice and patients with chronic hepatitis B virus infection[J]. Gastroenterology, 2012, 143(1): 188-198. e7. DOI: 10.1053/j.gastro.2012.03.044.
[12]	ZHAO J, ZHANG Z, LUAN Y, et al. Pathological functions of interleukin-22 in chronic liver inflammation and fibrosis with hepatitis B virus infection by promoting T helper 17 cell recruitment[J]. Hepatology, 2014, 59(4): 1331-1342. DOI: 10.1002/hep.26916.
[13]	ROLLA S, ALCHERA E, IMARISIO C, et al. The balance between IL-17 and IL-22 produced by liver-infiltrating T-helper cells critically controls NASH development in mice[J]. Clin Sci (Lond), 2016, 130(3): 193-203. DOI: 10.1042/CS20150405.
[14]	WU LY, LIU S, LIU Y, et al. Up-regulation of interleukin-22 mediates liver fibrosis via activating hepatic stellate cells in patients with hepatitis C[J]. Clin Immunol, 2015, 158(1): 77-87. DOI: 10.1016/j.clim.2015.03.003.
[15]	SERTORIO M, HOU X, CARMO RF, et al. IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections[J]. Hepatology, 2015, 61(4): 1321-1331. DOI: 10.1002/hep.27629.
[16]	BATALLER R, GAO B. Liver fibrosis in alcoholic liver disease[J]. Semin Liver Dis, 2015, 35(2): 146-156. DOI: 10.1055/s-0035-1550054.
[17]	KI SH, PARK O, ZHENG M, et al. Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: Role of signal transducer and activator of transcription 3[J]. Hepatology, 2010, 52(4): 1291-1300. DOI: 10.1002/hep.23837.
[18]	HENDRIKX T, DUAN Y, WANG Y, et al. Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice[J]. Gut, 2019, 68(8): 1504-1515. DOI: 10.1136/gutjnl-2018-317232.
[19]	NI YH, HUO LJ, LI TT. Antioxidant axis Nrf2-keap1-ARE in inhibition of alcoholic liver fibrosis by IL-22[J]. World J Gastroenterol, 2017, 23(11): 2002-2011. DOI: 10.3748/wjg.v23.i11.2002.
[20]	CHALASANI N, YOUNOSSI Z, LAVINE JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases[J]. Hepatology, 2018, 67(1): 328-357. DOI: 10.1002/hep.29367.
[21]	WANG X, OTA N, MANZANILLO P, et al. Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes[J]. Nature, 2014, 514(7521): 237-241. DOI: 10.1038/nature13564.
[22]	CHEN Z, DOWNING S, TZANAKAKIS ES. Four decades after the discovery of regenerating islet-derived (Reg) proteins: Current understanding and challenges[J]. Front Cell Dev Biol, 2019, 7: 235. DOI: 10.3389/fcell.2019.00235.
[23]	ZAI W, CHEN W, WU Z, et al. Targeted interleukin-22 gene delivery in the liver by polymetformin and penetratin-based hybrid nanoparticles to treat nonalcoholic fatty liver disease[J]. ACS Appl Mater Interfaces, 2019, 11(5): 4842-4857. DOI: 10.1021/acsami.8b19717.
[24]	ZHU J, ZHOU M, ZHAO X, et al. Blueberry, combined with probiotics, alleviates non-alcoholic fatty liver disease via IL-22-mediated JAK1/STAT3/BAX signaling[J]. Food Funct, 2018, 9(12): 6298-6306. DOI: 10.1039/c8fo01227j.
[25]	OH JH, SCHUELER KL, STAPLETON DS, et al. Secretion of recombinant interleukin-22 by engineered lactobacillus reuteri reduces fatty liver disease in a mouse model of diet-induced obesity[J]. mSphere, 2020, 5(3): e00183-20. DOI: 10.1128/mSphere.00183-20.
[26]	LI Y, TANG R, MA X. Epigenetics of primary biliary cholangitis[J]. Adv Exp Med Biol, 2020, 1253: 259-283. DOI: 10.1007/978-981-15-3449-2_10.
[27]	KAWATA K, TSUDA M, YANG GX, et al. Identification of potential cytokine pathways for therapeutic intervention in murine primary biliary cirrhosis[J]. PLoS One, 2013, 8(9): e74225. DOI: 10.1371/journal.pone.0074225.
[28]	HSUEH YH, CHANG YN, LOH CE, et al. AAV-IL-22 modifies liver chemokine activity and ameliorates portal inflammation in murine autoimmune cholangitis[J]. J Autoimmun, 2016, 66: 89-97. DOI: 10.1016/j.jaut.2015.10.005.
[29]	KONG X, FENG D, WANG H, et al. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice[J]. Hepatology, 2012, 56(3): 1150-1159. DOI: 10.1002/hep.25744.
[30]	HU BL, SHI C, LEI RE, et al. Interleukin-22 ameliorates liver fibrosis through miR-200a/beta-catenin[J]. Sci Rep, 2016, 6: 36436. DOI: 10.1038/srep36436.
[31]	MENG F, WANG K, AOYAMA T, et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice[J]. Gastroenterology, 2012, 143(3): 765-776. e3. DOI: 10.1053/j.gastro.2012.05.049.
[32]	CHOI Y, ABDELMEGEED MA, SONG BJ. Diet high in fructose promotes liver steatosis and hepatocyte apoptosis in C57BL/6J female mice: Role of disturbed lipid homeostasis and increased oxidative stress[J]. Food Chem Toxicol, 2017, 103: 111-121. DOI: 10.1016/j.fct.2017.02.039.