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<p>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.</p>

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Th17 cells require the DNA repair sensor xeroderma pigmentosum complementation Group C to control oxidative DNA damage in a murine model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月1日

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  • Jefferson Antônio Leite,
  • Natalia Notarberardino Bos,
  • Luísa Menezes-Silva,
  • Eloísa Martins da Silva,
  • Giovana da Silva Leandro,
  • Guilherme Comparotto Moreira de Goes,
  • Patrick da Silva,
  • Samuel Oliveira,
  • Eder Soares de Almeida Santos,
  • Hedden Ranfley,
  • Ilaria Palagi,
  • Magaiver Andrade-Silva,
  • Camila Pontes Ferreira,
  • José Arimatéa de Oliveira Nery Neto,
  • Victor Yuji Yariwake,
  • Marcella Cipelli,
  • Beatriz Leocata,
  • Talita Gonçalves,
  • Anthony Gabry da Silveira,
  • Sabrina Baroni,
  • Howard L. Weiner,
  • Thomas G. Hofmann,
  • Stefanie Scheu,
  • Bruno Junior Neves,
  • Nadja Cristhina de Souza-Pinto,
  • Leandro Machado Colli,
  • Ari Waisman,
  • Sandra Marcia Muxel,
  • Carlos Frederico Martins Menck,
  • Niels Olsen Saraiva Câmara

摘要

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.