期刊论文详细信息
Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society
IL-10 producing CD8 + CD122 + PD-1 + regulatory T cells are expanded by dendritic cells silenced for Allograft Inflammatory Factor-1
article
Diana M. Elizondo1  Temesgen E. Andargie1  Naomi L. Haddock1  Ricardo L. Louzada da Silva2  Tatiana Rodrigues de Moura2  Michael W. Lipscomb1 
[1] Department of Biology, Howard University;Laboratório de Biologia Molecular-Hospital Universitário, Universidade Federal de Sergipe-Aracaju
关键词: cytotoxic T cells;    dendritic cells;    programmed death-1;    suppression;    tolerogenic;    Tregs;   
DOI  :  10.1002/JLB.1A0118-010RR
学科分类:生理学
来源: Federation of American Societies for Experimental Biology
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【 摘 要 】

Allograft Inflammatory Factor-1 (AIF1) is a cytoplasmic scaffold protein that contains Ca2+ binding EF-hand and PDZ interaction domains important for mediating intracellular signaling complexes in immune cells. The protein plays a dominant role in both macrophage- and dendritic cell (DC)-mediated inflammatory responses. This study now reports that AIF1 expression in DC is important in directing CD8+ T cell effector responses. Silencing AIF1 expression in murine CD11c+ DC suppressed antigen-specific CD8+ T cell activation, marked by reduced CXCR3, IFN? and Granzyme B expression, and restrained proliferation. These primed CD8+ T cells had impaired cytotoxic killing of target cells in vitro. In turn, studies identified that AIF1 silencing in DC robustly expanded IL-10 producing CD8+ CD122+ PD-1+ regulatory T cells that suppressed neighboring immune effector responses through both IL-10 and PD-1-dependent mechanisms. In vivo studies recapitulated bystander suppression of antigen-responsive CD4+ T cells by the CD8+ Tregs expanded from the AIF1 silenced DC. These studies further demonstrate that AIF1 expression in DC serves as a potent governor of cognate T cell responses and present a novel target for engineering tolerogenic DC-based immunotherapies.

【 授权许可】

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