Elizondo Diana M, Andargie Temesgen E, Yang Dazhi, Kacsinta Apollo D, Lipscomb Michael W
Department of Biology, Howard University, Washington, DC, United States.
Department of Cellular and Molecular Medicine, UCSD School of Medicine, La Jolla, CA, United States.
Front Immunol. 2017 Nov 8;8:1502. doi: 10.3389/fimmu.2017.01502. eCollection 2017.
Allograft inflammatory factor-1 (AIF1) is a cytoplasmic scaffold protein shown to influence immune responses in macrophages and microglial cells. The protein contains Ca binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes. This study now reports that AIF1 is expressed in CD11c dendritic cells (DC) and silencing of expression restrains induction of antigen-specific CD4 T cell effector responses. AIF1 knockdown in murine DC resulted in impaired T cell proliferation and skewed polarization away from T helper type 1 and 17 fates. In turn, there was a parallel expansion of IL-10-producing and CD25Foxp3 T regulatory subsets. These studies are the first to demonstrate that AIF1 expression in DC serves as a potent governor of cognate T cell responses and presents a novel target for engineering tolerogenic DC-based immunotherapies.
同种异体移植炎症因子-1（AIF1）是一种细胞质支架蛋白，已证明其可影响巨噬细胞和小胶质细胞中的免疫反应。该蛋白包含对介导细胞内信号复合物很重要的钙结合EF手型结构域和PDZ相互作用结构域。本研究现报道，AIF1在CD11c树突状细胞（DC）中表达，表达沉默会抑制抗原特异性CD4 T细胞效应反应的诱导。小鼠DC中AIF1基因敲低导致T细胞增殖受损，并使极化偏离1型和17型辅助性T细胞命运。相应地，产生白细胞介素-10的和CD25Foxp3调节性T细胞亚群出现平行扩增。这些研究首次证明DC中AIF1的表达是同源T细胞反应的有效调控因子，并为设计基于耐受性DC的免疫疗法提供了一个新靶点。
