白细胞介素-22与肝脏疾病关系的研究进展

白细胞介素-22(IL-22)属于IL-10家族,可通过与膜受体复合物IL-22R1/IL-10R2结合而发挥作用。IL-22已被证实与溃疡性结肠炎等多种炎性疾病和自身免疫性疾病密切相关,并具有抗炎/促炎的双重作用。其与肝脏疾病的关系是近年来的研究热点,但目前仍存在不少争议,如在病毒性肝炎、原发性肝细胞癌(HCC)的不同阶段,IL-22表现出致病/保护不同的作用;对于不同病因引起的肝纤维化,其作用及相关机制也并不相同;但在酒精性肝病、肝再生、药物等引起的肝损伤中,其具有明确的肝脏保护作用。此文就IL-22在肝炎、肝纤维化、HCC、肝损伤等疾病中的作用及其相关机制作一综述。     

IL-22在肺部疾病中的研究进展

白细胞介素-22(Interleukin-22,IL-22)是IL-10家族的细胞因子,具有促进组织修复和维持组织完整性、调节先天免疫、促进抗微生物防御等生物学作用。已有许多研究证实,IL-22在感染、炎症、自身免疫性疾病和癌症中具有免疫调节功能,在这些研究模型中IL-22发挥的效应可能是病理性的,也可能是保护性的。IL-22与许多肺部疾病相关,如支气管哮喘、慢性阻塞性肺疾病、肺结核、肺癌等。随着IL-22在肺部疾病中的研究不断增加及深入,IL-22在肺部疾病中的作用也得到极大关注,本文就其研究进展做一综述。     

Th17细胞与Graves病及桥本甲状腺炎

Th17细胞是一种新近发现的Th细胞亚群,主要通过分泌白细胞介素(IL)-17、IL-21、IL-22、IL-6等细胞因子参与炎性反应、自身免疫性疾病、肿瘤等发生过程.近年来研究表明,Th17细胞及其所分泌的细胞因子在Graves病和桥本甲状腺炎的患者外周血单个核细胞中比例显著升高,提示Th17细胞可能在甲状腺疾病的发病机制中起重要作用.对Th17细胞不断深入的研究必将为甲状腺疾病的防治提供有益的帮助.     

白介素-12与克罗恩病

白介素-12(IL-12)是近年来发现的一种能特异性促进细胞免疫功能的细胞因子,在机体早期的固有性免疫和随后的适应性免疫应答中扮演重要角色.它在克罗恩病(CD)中也是一种重要的促炎细胞因子.此文综述IL-12的生物学概况、其在克罗恩病发病机制中的作用以及它在临床治疗领域中的应用.     

IL-27在结核性胸腔积液的诊断价值探讨

结核性胸腔积液(tuberculous pleural effusion,TPE)是一种临床呼吸科常见症状,是由多种细胞因子和多种细胞参与的病理性免疫反应.已有研究表明,与非TPE相比,TPE中腺苷脱氨酶、干扰素-γ、IL-27的含量显著增加.IL-27是最近发现的一种与IL-12相关的细胞因子,它由抗原提呈细胞产生,通过其对免疫反应的促炎和抗炎的双重作用调节各种免疫疾病.近年来,IL-27在TPE中的诊断价值的研究愈来愈受到关注.本文就IL-27的生物作用及其在TPE中诊断价值方面的研究进展作一综述.     

Th17细胞与肝脏疾病

辅助性T细胞(Th细胞)根据产生细胞因子和生物学功能分为Th1和Th2细胞.最近研究发现了一种与Th1和Th2细胞亚群不同的活化CD4+T细胞亚群-Th17细胞.TGF-β与IL-6或IL-21的协同作用,诱导Th17细胞分化.IL-12家族的IL-23在促进IL-17分泌、增强Th17细胞效应功能方面发挥重要作用,而RORγt是其特异性转录因子.分化成熟的Th17细胞可以分泌IL-17A、IL-17F、IL-21、IL-22、IL-6、TNF-α等多种细胞因子,在介导炎性反应(防御病原菌感染)、自身免疫性疾病、肿瘤、移植排斥反应等过程中发挥重要作用.Th17细胞也为研究肝脏疾病的发病机制及防治策略提供了新思路和方向.     

Th22细胞及其细胞因子IL-22与冠心病发病机制的研究进展

Th22是近几年新发现的一种辅助型T细胞亚群。Th22细胞及其主要的细胞因子白细胞介素22(IL-22)被证实在各种自身免疫疾病及慢性炎性疾病如类风湿性关节炎、银屑病、慢性异位性皮炎、哮喘、系统性硬化症等患者中均表达异常。然而关于Th22细胞及IL-22在冠心病中的作用及发病机制尚未明确。如能明确Th22及IL-22作用于冠心病的作用机制,可作为防治冠心病的新思路和新靶点。本文就Th22及其主要细胞因子IL-22的最新研究进展及临床应用现状做一全面综述。     

内毒素诱导的急性肺损伤早期炎症反应状态变化及其与肺损伤的关系

目的 观察内毒素(LPS)诱导的急性肺损伤(ALI)早期在肺组织局部和血浆中促炎因子白介素1β(IL-1β)、IL-6和抗炎因子IL-10、可溶性髓细胞触发受体-1(sTREM-1)的比值随时间的变化及其相关性以及与肺组织损伤、修复状态的关系.方法 建立LPS诱导的小鼠ALI模型,酶联免疫吸附法检测肺组织匀浆液以及血浆中IL-1β、IL-6、IL-10、sTREM-1的水平,并观察肺组织的损伤程度和修复状态.结果 LPS诱导的ALI过程中,肺组织局部以及血浆中抗炎因子IL-10和sTREM-1在注射LPS后1h均显著性升高,促炎因子IL-1β和IL-6的升高较前者缓慢,促炎/抗炎因子的比值随时间从低于正常比值到高于正常比值,逐渐升高,且在肺组织局部以及血浆中呈正相关.随时间推移,肺组织湿干重比值和肺组织匀浆液中总蛋白逐渐升高,肺组织损伤也进行性加重.结论 LPS诱导的ALI早期,炎症反应呈现从抗炎到促炎的变化趋势,且通过血浆中促炎/抗炎因子的比值可估计肺组织局部炎症反应状态.依此变化趋势进行治疗可能会得到更好的效果.     

IL-22和肠道干细胞在肠黏膜屏障中的作用

肠上皮细胞是肠黏膜屏障的重要组成部分,对维护机体的健康至关重要,肠黏膜屏障的维持和修复依赖于肠黏膜隐窝基底部干细胞的增殖和分化。近年来诸多IL-22相关研究显示,IL-22兼具抗炎和促炎作用,对肠上皮细胞的影响较为复杂,可促进或抑制肠黏膜屏障的修复。该文主要就近年来IL-22和肠道干细胞在肠黏膜屏障中作用的相关研究进展作一综述。     

038 白介素-10对急性肺损伤的保护作用

白介素-10(IL-10)是一个有力的抗炎因子,它抑制主要的炎症因子和趋化因子的合成,抑制细胞介导的免疫反应,同时上调部分抗炎因子,故有望在急性肺损伤治疗中发挥重要作用.本文就其分子结构、细胞分布、免疫作用、自身表达调节及与急性肺损伤的关系作一综述.     

白介素-22在慢性代谢性疾病中的研究进展

目的 白介素-22(IL-22)是IL-10细胞因子家族成员,可以由多种免疫细胞分泌。IL-22受体(IL-22R)主要在非造血源性内皮细胞和基质细胞中表达,IL-22通过与IL-22R结合在黏膜屏障防御、组织修复、上皮细胞存活和增殖中发挥重要作用。IL-22的表达与多种代谢性疾病密切相关,是近年来代谢领域研究的热点。本文就IL-22在脂肪性肝病、肥胖、糖尿病等慢性代谢性疾病中的研究进展进行综述。     

Th22细胞研究的新进展

Th22细胞亚群是新发现的一类T细胞亚群,分泌白细胞介素-22、白细胞介素-13、白介素-6等细胞因子,而不产生干扰素-r、白细胞介素-4和白细胞介素-17。其功能主要通过白细胞介素-22来实现,介导炎症反应、自身免疫性疾病、肿瘤等的发生发展,在机体免疫调节、宿主防御及组织修复中发挥重要作用。该文对Th22细胞的研究进展作一简要综述。     

白细胞介素22在结核性胸膜炎与恶性胸腔积液中生物学特性的研究进展

白细胞介素22（IL-22）是IL-10细胞因子家族成员之一,通过与IL-22R1、IL-10R2二聚体结合发挥作用。主要由T辅助细胞(T-helper cell)22（Th22）、Th17和Th1细胞表达,部分自然杀伤细胞（NK细胞）、γδT（T细胞受体的一种）细胞和淋巴组织可诱导（LTi）细胞也可表达。结核性胸腔积液和恶性胸腔积液中都存在显著升高的IL-22,主要来源于受趋化因子作用募集于胸膜腔的外周血CD4⁺ T淋巴细胞和胸膜腔局部在IL-6、IL-23、IL-1β和肿瘤坏死因子-α（TNF-α）等细胞因子作用下分化而来的CD4⁺ T细胞。在胸膜腔中,IL-22通过促进基质金属蛋白酶（matrix metalloproteinases,MMPs）的表达发挥免疫病理作用,并通过介导NK细胞产生溶解因子减少寄生于单核细胞来源的巨噬细胞内的结核分枝杆菌生长。在恶性胸腔积液中,IL-22可通过促进肿瘤细胞增殖、迁移,并且通过增加黏附分子的表达促进与胸膜间皮细胞（pleural mesothelial cells,PMCs）的黏附发挥作用。研究IL-22在上述两种疾病中的作用机制,将会为免疫诊断与治疗开辟新的途径。     

Different Th17 immunity in gut,liver, and adipose tissues during obesity: the role of diet,genetics, and microbes

Microbes modify immunometabolism responses linking obesity and type 2 diabetes. Immunity helps maintain a host-microbe symbiosis, but inflammation can promote insulin resistance in tissues that control blood glucose. We were interested in compartmentalization of immune responses during obesity and show here that feeding mice an obesity-causing high-fat diet (HFD) decreased a marker of neutrophil activation and cytokines related to Th17 responses in the gut. A HFD decreased IL-17 and IL-21/22 in the ileum and colon, respectively. A HFD increased IL-17, IL-21/22 and other related Th17 responses in the liver. At the whole tissue level, there is divergence in gut and metabolic tissue Th17 cytokines during diet-induced obesity. Deletion of the bacterial peptidoglycan sensor NOD2 had relatively minor effects on these immune responses. We propose a model where diet-induced obesity promotes a permissive gut immune environment and sets the stage for host genetics to contribute to dysbiosis-driven metabolic tissue inflammation.     

Interleukin-22 ameliorates acute severe pancreatitisassociated lung injury in mice

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.     

Expression of interleukin-22/STAT3 signaling pathway in ulcerative colitis and related carcinogenesis

AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.     

Role of regenerating islet-derived proteins in inflammatory bowel disease

Inflammatory bowel disease(IBD) is an inflammatory disorder of the gastrointestinal tract that affects millions of patients worldwide. It has a complex and multifactorial etiology leading to excessive exposure of intestinal epithelium to microbial antigens, inappropriate activation of the immune system and ultimately to the damage of intestinal tissues. Although numerous efforts have been made to improve the disease management, IBD remains persistently recurring and beyond cure. This is due largely to the gaps in our understanding of the pathogenesis of IBD that hamper the development of timely diagnoses and effective treatment. However, some recent discoveries, including the beneficial effects of interleukin-22(IL-22) on the inflamed intestine, have shed light on a self-protective mechanism in IBD. Regenerating islet-derived(REG/Reg) proteins are small secretory proteins which function as IL-22's downstream effectors.Mounting studies have demonstrated that IBD patients have significantly increased REG expressions in the injured intestine, but with undefined mechanisms and roles. The reported functions of REG/Reg proteins in intestinal homeostasis, such as those of antibacterial, anti-inflammatory and tissue repair,lead us to discuss their potential mechanisms and clinical relevance in IBD in order to advance IBD research and management.     

Elevated circulating levels of IL-21 and IL-22 define a cytokine signature profile in type 2 autoimmune hepatitis patients

Background and aims. Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver in which the immunological mechanisms involved in tissue destruction and/or repair are still unclear. Different pro-inflammatory cytokines have been shown to play a determinant role in AIH pathogenesis. Here, we aim to compare the circulating levels of pro-and anti-inflammatory cytokines such as IL-6, TNF-α, IL-17A/F, IL-21, IL-22, IL-23, and IL-10 in patients with type 2 AIH compared to patients with type 1 AIH and healthy controls (HC). Fourty-six Mexican patients with AIH were recruited in our study. Patients were classified as type 1 or 2 AIH based on immune serological markers. Fourty-four serum samples from healthy individuals were included as controls. Serum cytokine levels were determined by ELISA technique.Results. Compared to healthy controls, serum levels of IL-17F, IL-21, IL-23, IL-10, IL-6, and TNF-α, but not IL-17A and IL-22, were significantly increased in AIH patients. When patients were grouped by aminotransferase activity, a biomarker of active disease, a positive correlation between serum IL-17F and alanine transaminase (rs: 0.4739; P = 0.0009) and aspartate transaminase (rs: 0.4984; P = 0.0004) levels was found. A cytokine signature profile associated with type 2 AIH was characterized by high serum IL-21 (type 1 AIH: 0.66 pg/mL; type 2 AIH: 331.1 pg/mL; P = 0.0042) and IL-22 (type 1 AIH: 0.1 pg/mL; type 2 AIH: 55.26 pg/mL; P = 0.0028) levels.Conclusions. We show for the first time, differential regulation of certain pro-inflammatory cytokines associated with disease progression and AIH type in Mexican patients.     

Bidirectional roles of IL-22 in the pathogenesis of allergic airway inflammation

Asthma is the most prevalent allergic disease of the airway, which is characterized by eosinophilic inflammation, mucus hyperproduction, and airway hyper-responsiveness. Although these pathognomonic features are mainly mediated by antigen-specific Th2 cells and their cytokines, such as IL-4, IL-5, and IL-13, recent studies have revealed that other inflammatory cells, including Th17 cells and innate lymphoid cells (ILCs), also play a critical role in the pathogenesis of asthma. IL-22, one of the cytokines produced by Th17 cells and type 3 ILCs, has distinct functional properties, as IL-22 exclusively acts on non-hematopoietic cells including epithelial cells of mucosal surface and exhibits a broad range of action in regeneration and host protection. In accordance with the fact that lung epithelial cells play a critical role in the pathogenesis of asthma, we and other groups have shown that IL-22 is involved in the regulation of allergic airway inflammation. In this review, we discuss recent advances in the biology of IL-22 and its involvement in the pathogenesis of allergic airway inflammation.