白细胞介素 35 和转化生长因子-β调节内脏利什曼病中 Th17 细胞的效应功能。
Effector functions of Th17 cells are regulated by IL-35 and TGF-β in visceral leishmaniasis.
机构信息
Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata, India.
Department of Medicine, Albert Einstein College of Medicine/ Montefiore Medical Center, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
出版信息
FASEB J. 2021 Sep;35(9):e21755. doi: 10.1096/fj.202002356RR.
Visceral leishmaniasis (VL) is a debilitating human pathogenesis in which the body's immune functions are severely compromised. Various subsets of T cells, including Th17 cells are important regulators of immune responses observed in various pathologies. The role of Th17 cells and its correlation with immuno-regulatory cytokines are however not well understood in human VL. Herein we studied how IL-17 is associated with the progression of Leishmania donovani infection using murine model of VL. We found induction of a strong IL-17 response at the early phase of infection which progressively reduced to basal level during chronic VL. The mechanistic study of this behavior was found to be linked with the role of regulatory T cells (CD4 CD25 T cells) that suppresses the proliferation of the Th17 cell population. Moreover, TGF-β and IL-35 derived from CD4 CD25 T cells are the key mediators for the downregulation of IL-17 during chronic VL. Thus, this study points to an antagonistic effect of Tregs and Th17 cells that can be used for designing better therapeutic and preventive strategies against leishmaniasis.
内脏利什曼病(VL)是一种使人虚弱的人体发病机制,其中身体的免疫功能受到严重损害。包括 Th17 细胞在内的各种 T 细胞亚群是各种病理中观察到的免疫反应的重要调节剂。然而,Th17 细胞的作用及其与免疫调节细胞因子的相关性在人类 VL 中尚未得到很好的理解。在此,我们使用 VL 的小鼠模型研究了 IL-17 如何与利什曼原虫感染的进展相关。我们发现,在感染的早期阶段诱导了强烈的 IL-17 反应,而在慢性 VL 期间逐渐降低到基础水平。对这种行为的机制研究发现与调节性 T 细胞(CD4 CD25 T 细胞)的作用有关,调节性 T 细胞抑制 Th17 细胞群体的增殖。此外,来自 CD4 CD25 T 细胞的 TGF-β 和 IL-35 是慢性 VL 期间下调 IL-17 的关键介质。因此,这项研究指出了 Treg 和 Th17 细胞的拮抗作用,可用于设计针对利什曼病的更好的治疗和预防策略。