Lymphotoxin limits Foxp3⁺ regulatory T cell development from Foxp3^lo precursors via IL-4 signaling.

ABSTRACT: Regulatory T cells (T_reg) are critical players of immune tolerance that develop in the thymus via two distinct developmental pathways involving CD25⁺Foxp3^- and CD25^-Foxp3^lo precursors. However, the mechanisms regulating the recently identified Foxp3^lo precursor pathway remain unclear. Here, we find that the membrane-bound lymphotoxin α₁β₂ (LTα₁β₂) heterocomplex is upregulated during T_reg development upon TCR/CD28 and IL-2 stimulation. We show that Lta expression limits the maturational development of T_reg from Foxp3^lo precursors by regulating their proliferation, survival, and metabolic profile. Transgenic reporter mice and transcriptomic analyses f

SUBMITTER: Borelli A 

PROVIDER: S-EPMC11324892 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature