AIM2 promotes TH17 cells differentiation by regulating RORγt transcription activity

被引：2

作者：

Leite, Jefferson Antonio ^{[1
,4
,7
]}

Menezes, Luisa ^{[4
]}

Martins, Eloisa ^{[4
,5
]}

Rodrigues, Tamara Silva ^{[1
,3
]}

Tavares, Lucas ^{[3
]}

Ebering, Anna ^{[7
]}

Schelmbauer, Carsten ^{[7
]}

Cebinelli, Guilherme C. Martelossi ^{[1
,2
]}

Zinina, Valeriya ^{[7
]}

Golden, Artemiy ^{[7
]}

Soshnikova, Natalia ^{[7
]}

Zamboni, Dario S. ^{[3
]}

Cunha, Fernando Q. ^{[2
]}

Huber, Magdalena ^{[8
]}

Silva, Joao Santana ^{[1
,6
]}

Waisman, Ari ^{[7
]}

Carlos, Daniela ^{[1
]}

Camara, Niels Olsen Saraiva ^{[1
,4
,5
]}

机构：

[1] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, Ribeirao Preto, SP, Brazil

[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pharmacol, Ribeirao Preto, SP, Brazil

[3] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Cellular & Mol Biol & Pathogen Bioagents, Ribeirao Preto, SP, Brazil

[4] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo, Brazil

[5] Univ Fed Sao Paulo, Sch Med, Div Nephrol, Sao Paulo, Brazil

[6] Univ Sao Paulo, Fiocruz Bi Inst Translat Med Project, Biinst Translat Med Project, Ribeirao Preto, SP, Brazil

[7] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Mol Med, Mainz, Germany

[8] Univ Marburg, Inst Syst Immunol, Ctr Tumor Biol & Immunol, Marburg, Germany

来源：

ISCIENCE | 2023年 / 26卷 / 11期

基金：

巴西圣保罗研究基金会;

关键词：

INFLAMMASOME; TUMORIGENICITY; HIN-200; FAMILY; DEATH; GENE;

D O I：

10.1016/j.isci.2023.108134

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (ROR gamma t, IL-1R1, IL-23R). AIM2 is located in the nucleus of Th17 cells, where it interacts with ROR gamma t, 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.

引用

页数：19

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