Expanded GATA3⁺ T regulatory cells fail to control germinal center responses during pulmonary fibrosis in humans and mice

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B1000
Abstract ID: 5966

Presenting Author:
Tania E Velez , Postdoctoral Fellow at Univ. of Virginia

Abstract:

Interstitial lung disease (ILD) describes heterogenous conditions of progressive lung fibrosis. Interestingly, lung lymph nodes (LLN) of different types of ILD patients are enlarged and predicts survival outcomes. Our recent studies demonstrate that there are active germinal centers (GC) in the LLN of ILD patients, suggesting on-going antigen-specific responses. To determine whether these responses are dysregulated, we investigated T regulatory cells (Tregs). Our data shows that Tregs are expanded in the LLN of all ILD patients compared to controls. Intriguingly, there was a predominance of GATA3⁺ Tregs that co-expressed ICOS and CD137, indicating recent activation. GATA3⁺ Tregs can have detrimental effects in asthma models, but their role in pulmonary fibrosis is unknown. Thus, we hypothesize that GATA3⁺ Tregs in ILD patients may be failing to control GC responses and potentially facilitating lung fibrosis. To test this hypothesis, we utilized a mouse model of bleomycin (bleo)-induced pulmonary fibrosis. We find that GATA3⁺ Tregs expand in the lung and mediastinal LN (mdLN) of bleo-treated mice, and there is evidence of GC responses. Depletion of all Tregs is detrimental and leads to enlargement of mdLN. In contrast, specific depletion of GATA3 in Tregs is protective and does not lead to mdLN enlargement. In summary, these data show that GATA3⁺ Tregs may have roles in promoting pathogenic mechanisms during pulmonary fibrosis in humans and mice.