Leite Jefferson Antônio, Menezes Luísa, Martins Eloisa, Rodrigues Tamara Silva, Tavares Lucas, Ebering Anna, Schelmbauer Carsten, Martelossi Cebinelli Guilherme C, Zinina Valeriya, Golden Artemiy, Soshnikova Natalia, Zamboni Dario S, Cunha Fernando Q, Huber Magdalena, Silva João Santana, Waisman Ari, Carlos Daniela, Saraiva Câmara Niels Olsen
Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
iScience. 2023 Oct 4;26(11):108134. doi: 10.1016/j.isci.2023.108134. eCollection 2023 Nov 17.
AIM2 is an interferon-inducible HIN-200 protein family member and is well-documented for its roles in innate immune responses as a DNA sensor. Recent studies have highlighted AIM2's function on regulatory T cells (Treg) and follicular T cells (Tfh). However, its involvement in Th17 cell differentiation remains unclear. This study reveals that AIM2 promotes Th17 cell differentiation. AIM2 deficiency decreases IL-17A production and downregulates key Th17 associated proteins (RORγt, IL-1R1, IL-23R). AIM2 is located in the nucleus of Th17 cells, where it interacts with RORγt, enhancing its binding to the Il17a promoter. The absence of AIM2 hinders naive CD4 T cells from differentiating into functional Th17 cells and from inducing colitis in Rag1 mice. This study uncovers AIM2's role as a regulator of Th17 cell transcriptional programming, highlighting its potential as a therapeutic target for Th17 cell-mediated inflammatory diseases.
AIM2是一种干扰素诱导的HIN-200蛋白家族成员，作为一种DNA传感器，其在先天免疫反应中的作用已有充分记载。最近的研究突出了AIM2在调节性T细胞（Treg）和滤泡辅助性T细胞（Tfh）上的功能。然而，其在Th17细胞分化中的作用仍不清楚。本研究揭示AIM2促进Th17细胞分化。AIM2缺陷会降低IL-17A的产生，并下调关键的Th17相关蛋白（RORγt、IL-1R1、IL-23R）。AIM2定位于Th17细胞的细胞核中，在那里它与RORγt相互作用，增强其与Il17a启动子的结合。AIM2的缺失阻碍了初始CD4 T细胞分化为功能性Th17细胞以及在Rag1小鼠中诱导结肠炎。本研究揭示了AIM2作为Th17细胞转录编程调节因子的作用，突出了其作为Th17细胞介导的炎症性疾病治疗靶点的潜力。
