AIM2 promotes TH17 cells differentiation by regulating RORγt transcription activity

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

doi:10.1016/j.isci.2023.108134

AIM2 promotes T_H17 cells differentiation by regulating RORγt transcription activity

iScience. 2023 Oct 4;26(11):108134. doi: 10.1016/j.isci.2023.108134. eCollection 2023 Nov 17.

Authors

Jefferson Antônio Leite^{1

2

3}, Luísa Menezes², Eloisa Martins^{2

4}, Tamara Silva Rodrigues^{1

5}, Lucas Tavares⁵, Anna Ebering³, Carsten Schelmbauer³, Guilherme C Martelossi Cebinelli^{1

6}, Valeriya Zinina³, Artemiy Golden³, Natalia Soshnikova³, Dario S Zamboni⁵, Fernando Q Cunha⁶, Magdalena Huber⁷, João Santana Silva^{1

8}, Ari Waisman³, Daniela Carlos¹, Niels Olsen Saraiva Câmara^{1

2

4}

Affiliations

¹ Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
² Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
³ Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
⁴ Division of Nephrology, School of Medicine, Federal University of São Paulo, São Paulo, Brazil.
⁵ Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
⁶ Department of Pharmacology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
⁷ Institute of Systems Immunology, Center for Tumor and Immunology, University of Marburg, Marburg, Germany.
⁸ Fiocruz-Bi-Institutional Translational Medicine Project, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

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 (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.

Keywords: Biological sciences; Cell biology.