Treg dysregulation in the oxidative lung milieu: an emerging mechanistic link in interstitial lung disease associated with systemic autoimmune rheumatic diseases.

Systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD) is a fatal complication, in which the progression of pulmonary fibrosis has been closely linked to immune microenvironment imbalance and oxidative stress. Regulatory T cells (Tregs), as a central component of immune tolerance, play a crucial role in suppressing excessive inflammation. Current evidence suggests that oxidative stress may contribute to Treg dysregulation through several interrelated mechanisms, including redox-sensitive regulation of Foxp3 expression and stability, disruption of IL-2 signaling, and remodeling of the inflammatory microenvironment. However, the majority of the mechanistic evidence is derived from experimental models or related autoimmune and inflammatory conditions, with limited direct validation in patients with SARD-ILD. These proposed interactions may contribute to a self-reinforcing cycle of oxidative stress and Treg dysregulation, potentially promoting effector T-cell activation, fibroblast proliferation, and imbalanced inflammation and repair, thereby contributing to pulmonary fibrotic remodeling. This review integrates current evidence on the potential links among oxidative stress, Treg dysregulation, and pulmonary fibrosis in SARD-ILD, and proposes an emerging mechanistic framework to guide further investigation into their possible interactions and therapeutic implications.