Th17 cells require the DNA repair sensor xeroderma pigmentosum complementation Group C to control oxidative DNA damage in a murine model
T helper 17 cells play essential roles in mucosal immunity and autoimmunity, yet the mechanisms that protect these cells from oxidative DNA damage remain poorly defined. Here we show, in a murine model, that the nucleotide excision repair sensor Xeroderma Pigmentosum Complementation Group C preserves genomic stability and metabolic fitness during T helper 17 cell differentiation. Loss of this factor reduces interleukin 17 production and increases mitochondrial reactive oxygen species and oxidative DNA damage, resulting in altered metabolic programs. Mechanistically, Xeroderma Pigmentosum Complementation Group C interacts with the base excision repair enzyme 8-oxoguanine DNA glycosylase, and its absence enhances oxidative lesion incision activity, indicating defective coordination between DNA repair pathways. Restoring antioxidant capacity rescues cytokine production and limits DNA damage in deficient cells. Together, these findings identify Xeroderma Pigmentosum Complementation Group C as a key coordinator of DNA repair and redox control required for T helper 17 cell function in inflammatory settings.
Authors
- Jefferson Antônio Leite (ORCID: https://orcid.org/0000-0002-9437-5393)
- Giovana da Silva Leandro (ORCID: https://orcid.org/0000-0003-0063-3601)
- Marcella Cipelli (ORCID: https://orcid.org/0000-0001-9185-3938)
- Leandro M. Colli (ORCID: https://orcid.org/0000-0001-6928-1195)
- Patrick da Silva (ORCID: https://orcid.org/0000-0002-3481-4972)
- Sabrina Baroni (ORCID: https://orcid.org/0000-0002-2605-3544)
- Talita Mota Gonçalves (ORCID: https://orcid.org/0000-0003-4625-8376)
- Ari Waisman (ORCID: https://orcid.org/0000-0003-4304-8234)
- Hedden Ranfley (ORCID: https://orcid.org/0000-0002-5683-4173)
- Camila Pontes Ferreira (ORCID: https://orcid.org/0000-0002-3835-2197)
- Eloísa Martins da Silva (ORCID: https://orcid.org/0000-0002-2230-8810)
- Sandra Márcia Muxel (ORCID: https://orcid.org/0000-0003-0118-5361)
- Stefanie Scheu (ORCID: https://orcid.org/0000-0002-9707-8191)
- Victor Yuji Yariwake (ORCID: https://orcid.org/0000-0003-0639-1228)
- Magaiver Andrade-Silva (ORCID: https://orcid.org/0000-0001-5135-0981)
- Luísa Menezes-Silva (ORCID: https://orcid.org/0000-0002-6860-6522)
- Carlos Frederico Martins Menck (ORCID: https://orcid.org/0000-0003-1941-0694)
- Ilaria Palagi
- S. A. Oliveira
- Beatriz Leocata
- Anthony Gabry da Silveira
- Niels Olsen Saraiva Câmara
- Nadja Cristhina de Souza-Pinto
- Natalia Notarberardino Bos
- Bruno Junior Neves
- Howard L. Weiner
- José Arimatéa de Oliveira Nery Neto
- Guilherme Comparotto Moreira de Goes
- Eder Soares de Almeida Santos
Institutions
- Universidade Federal do Rio de Janeiro (BR)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Universidade de São Paulo (BR)
- Johannes Gutenberg University Mainz (DE)
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Institute of Biomedical Science (GB)
- University of Rostock (DE)
- Universidade Federal de Goiás (BR)
- Universidade Federal de São Paulo (BR)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-01
- DOI
- https://doi.org/10.1038/s41467-026-69914-y
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado de Goiás
- Universidade de São Paulo