小柯机器人

美国纽约大学医学院Dan R. Littman研究团队发现血清淀粉样蛋白A蛋白（SAA）诱导致病性Th17细胞并促进炎性疾病的发生。相关论文2019年12月19日发表在国际学术期刊《细胞》上。

研究人员表示SAA可以指导病原性促炎性Th17细胞分化过程，与STAT3激活细胞因子协同直接作用于T细胞。使用功能丧失和功能获得的小鼠模型，他们表示SAA1，SAA2和SAA3在促进Th17介导的炎症性疾病中具有独特的系统和局部功能。这些研究表明，由SAA调节的T细胞信号传导途径可能是抗炎疗法的诱人靶标。

据悉，产生白介素（IL）-17细胞因子的淋巴样细胞可保护屏障组织免受病原微生物的侵害，但它们也是炎症和自身免疫性疾病的重要效应器。由依赖于RORγt产生的IL-17A和IL-17F所定义的T辅助17（Th17）细胞在从原始CD4 + T细胞进行微生物群定向分化后，在肠道中发挥体内稳态功能。在非致病性环境中，它们的细胞因子产生受到相邻肠上皮细胞分泌的血清淀粉样蛋白A蛋白（SAA1和SAA2）的调节。但是，Th17细胞的行为根据其环境而显著不同。

附：英文原文

Title: Serum Amyloid A Proteins Induce Pathogenic Th17 Cells and Promote Inflammatory Disease

Author: June-Yong Lee, Jason A. Hall, Lina Kroehling, Lin Wu, Tariq Najar, Henry H. Nguyen, Woan-Yu Lin, Stephen T. Yeung, Hernandez Moura Silva, Dayi Li, Ashley Hine, P’ng Loke, David Hudesman, Jerome C. Martin, Ephraim Kenigsberg, Miriam Merad, Kamal M. Khanna, Dan R. Littman

Issue&Volume: December 19, 2019

Abstract: Lymphoid cells that produce interleukin (IL)-17 cytokines protect barrier tissuesfrom pathogenic microbes but are also prominent effectors of inflammation and autoimmunedisease. T helper 17 (Th17) cells, defined by RORγt-dependent production of IL-17Aand IL-17F, exert homeostatic functions in the gut upon microbiota-directed differentiationfrom naive CD4+ T cells. In the non-pathogenic setting, their cytokine production is regulated byserum amyloid A proteins (SAA1 and SAA2) secreted by adjacent intestinal epithelialcells. However, Th17 cell behaviors vary markedly according to their environment.Here, we show that SAAs additionally direct a pathogenic pro-inflammatory Th17 celldifferentiation program, acting directly on T cells in collaboration with STAT3-activatingcytokines. Using loss- and gain-of-function mouse models, we show that SAA1, SAA2,and SAA3 have distinct systemic and local functions in promoting Th17-mediated inflammatorydiseases. These studies suggest that T cell signaling pathways modulated by the SAAsmay be attractive targets for anti-inflammatory therapies.

DOI: 10.1016/j.cell.2019.11.026

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31283-8