Work

GATA3-expressing Tregs are detrimental during lung injury 3861

Year: 2025

Type: article

Abstract: Description Interstitial lung disease (ILD) is a rare but deadly disease of progressive fibrosis in the lung. While there are heterogenous etiologies of ILD, there is a common phenomenon where enlarged lung lymph nodes (LLN) predict survival outcomes. To determine whether responses in the LLN could drive pathogenesis in the lung, we first interrogated the cellular populations in the LLN of ILD patients compared to controls. Interestingly, T regulatory cells (Tregs) were the only cell population that was significantly elevated compared to controls, and there was an enrichment of recently activated ICOS+CD137+GATA3+ Tregs in the ILD patients’ LLN. To determine whether GATA3+ Tregs are involved in disease pathogenesis, we utilized a mouse model of bleomycin (bleo)-induced lung injury and pulmonary fibrosis. In response to bleo-treatment, GATA3+ Tregs expand in the lung and mediastinal LN. Depletion of all Tregs results in death during lung injury, however specific depletion of GATA3+ Tregs protected mice from mortality during lung injury. Depleting GATA3+ Tregs after the lung injury phase had no effect in survival or fibrosis, but unexpectedly, there was an increase of tertiary structures in the lung tissue. These data suggest a dichotomy of Treg responses dependent on specific subsets and disease state where GATA3+ Tregs are detrimental during lung injury and regulate formation of tertiary structures during lung fibrosis. Funding Sources T32 AI007090; AHA 835938; T32 AI007496 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.1613