AIM2 promotes T_H17 cells differentiation by regulating RORγt transcription activity

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Leite, Jefferson Antonio ; Menezes, Luisa ; Martins, Eloisa ; Rodrigues, Tamara Silva ; Tavares, Lucas ; Ebering, Anna ; Schelmbauer, Carsten ; Cebinelli, Guilherme C. Martelossi ; Zinina, Valeriya ; Golden, Artemiy ; Soshnikova, Natalia ; Zamboni, Dario S. ; Cunha, Fernando Q. ; Huber, Magdalena ; Silva, Joao Santana ; Waisman, Ari ; Carlos, Daniela ; Camara, Niels Olsen Saraiva

• Document type: Journal article
• Source: ISCIENCE; v. 26, n. 11, p. 19-pg., 2023-10-14.

Abstract

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. (AU)

• FAPESP's process: 18/14815-0 - Evaluation of the intestinal microbioma profile and of the therapeutic potential of intervention strategies in the immunopathogeny of type 1 and 2 Diabetes
• Grantee: Daniela Carlos Sartori
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology
• Grantee: Niels Olsen Saraiva Câmara
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• FAPESP's process: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg)
• Grantee: Carlos Frederico Martins Menck
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