PGC1α-mediated mitochondrial fitness promotes Treg cell differentiation

Author(s)

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

• Document type: Journal article
• Source: Cellular Immunology; v. 414, p. 7-pg., 2025-08-01.

Abstract

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)

• FAPESP's process: 22/10585-5 - Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1a) at the interface between mitochondrial activity, regulatory T cell biology and Cancer
• Grantee: Luis Eduardo Alves Damasceno
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 21/00408-6 - Center for Research in Immuno-Oncology (CRIO)
• Grantee: Kenneth John Gollob
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 22/08412-5 - Understanding the molecular regulation of Th17 and regulatory T cells in infections and autoimmune diseases
• Grantee: José Carlos Farias Alves Filho
• Support Opportunities: Regular Research Grants