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
Affiliations
Jefferson Antônio Leite
Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil; Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Corresponding author
Luísa Menezes
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil
Eloisa Martins
Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil; Division of Nephrology, School of Medicine, Federal University of São Paulo, São Paulo, Brazil
Tamara Silva Rodrigues
Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
Lucas Tavares
Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
Anna Ebering
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
Carsten Schelmbauer
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
Guilherme C. Martelossi Cebinelli
Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Pharmacology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
Valeriya Zinina
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
Artemiy Golden
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
Natalia Soshnikova
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany
Dario S. Zamboni
Department of Cellular and Molecular Biology and Pathogenic Bioagents, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
Fernando Q. Cunha
Department of Pharmacology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
Magdalena Huber
Institute of Systems Immunology, Center for Tumor and Immunology, University of Marburg, Marburg, Germany
João Santana Silva
Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Fiocruz-Bi-Institutional Translational Medicine Project, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
Ari Waisman
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany; Corresponding author
Daniela Carlos
Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Corresponding author
Niels Olsen Saraiva Câmara
Department of Biochemistry and Immunology, Ribeirão Preto School of Medicine, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil; Division of Nephrology, School of Medicine, Federal University of São Paulo, São Paulo, Brazil; Corresponding author
Summary: 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.
