Mucosal Immunol. 2025 Aug 21:S1933-0219(25)00089-3. doi: 10.1016/j.mucimm.2025.08.006. Online ahead of print.
ABSTRACT
Genital inflammation is associated with increased HIV risk. We previously found that endocervical Tregs correlated with decreased genital inflammation and reduced HIV target cells. IL-2 induces Tregs, and efforts to potentiate its regulatory activities clinically are ongoing. In this study, intraperitoneal administration of IL-2 conjugated to IL-2mAb clone JES6-1A12 (IL2C-trimeric) in estrous-synchronized female FoxP3GFP mice selectively expanded Tregs in the lower female genital tract, with limited effects on non-Treg cells. IL2C-trimeric increased the expression of GITR on Tregs, and most Tregs expressed tissue residency markers. IL2C-trimeric pre-treatment prevented neutrophil influx during vaginal challenge with both nonoxynol-9 (N-9) and Mobiluncus mulieris, but maintenance of E-cadherin expression and barrier integrity was only observed for M. mulieris and not N-9. Depletion of FoxP3+Tregs reversed the protective effects of IL2C-trimeric. Thus, induction of Tregs could be a potential strategy to regulate genital inflammation, reduce HIV acquisition risk, and improve reproductive health outcomes in women.
PMID:40848948 | DOI:10.1016/j.mucimm.2025.08.006