PGC1α-mediated mitochondrial fitness promotes Treg cell differentiation

Autor(es)

Damasceno, Luis Eduardo Alves ; Barbosa, Gabriel Alberto de Carvalho ; Sparwasser, Tim ; Cunha, Thiago Mattar ; Cunha, Fernando Queiroz ; Alves-Filho, Jose Carlos

• Tipo de documento: Artigo Científico
• Fonte: Cellular Immunology; v. 414, p. 7-pg., 2025-08-01.

Resumo

Regulatory T (Treg) cells play a critical role in the maintenance of immune tolerance to self-antigens and suppression of excessive immune responses. They employ a distinct metabolic profile from other CD4 T cell subsets to support their differentiation and suppressive function, which is characterized by enhanced mitochondrial metabolism. Although PGC1 alpha is considered a master regulator of mitochondrial biogenesis and function, its role in Treg cell differentiation remains unclear. Herein, we demonstrated that PGC1 alpha is highly expressed in Treg cells compared to other CD4 T cell populations. Using a pharmacological approach, we found that its transcriptional activation in iTreg cells enhanced mitochondrial fitness, characterized by increased expression of mitochondrial genes, mitochondrial mass, and metabolic activity. Moreover, PGC1 alpha activation enhanced both mouse and human iTreg cell differentiation, while its inhibition reduced this process. Therefore, our findings shed light on the potential role of PGC1 alpha as a pharmacological target when manipulating Treg cells as a therapeutic strategy. (AU)

• Processo FAPESP: 22/10585-5 - Coativador 1-alfa do receptor gama ativado por proliferador do peroxissoma (PGC1a) na interface entre atividade mitocondrial, biologia de células T reguladoras e Câncer
• Beneficiário: Luis Eduardo Alves Damasceno
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 21/00408-6 - Centro para Pesquisa em Imuno-Oncologia (CRIO)
• Beneficiário: Kenneth John Gollob
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 22/08412-5 - Investigando os mecanismos moleculares das células Th17 e T reguladoras nos processos infecciosos e autoimunes
• Beneficiário: José Carlos Farias Alves Filho
• Modalidade de apoio: Auxílio à Pesquisa - Regular