Proteomic insights into human induced regulatory T cells: the role of LPXN and CD160 in immune suppression 

ABSTRACT

Regulatory T cells (Treg) play a central role in maintaining immune homeostasis, and the implementation of in vitro induced Treg cells (iTreg) to control immune function has significant potential in clinical medicine. The clinical application of iTreg has been limited by their poor stability. To better define the molecular characteristics of human iTreg, we performed a data-independent acquisition proteomics, detecting over 8000 proteins and providing a quantitative comparison of their relative levels in iTreg and activated Th0 cells. Consistent with the known molecular characteristics of Treg, several Treg signature proteins, including FOXP3, IKZF4, IL2RA, CTLA4, PD-1, IKZF3, LAG3, RUNX1 and HIC1, were identified and validated using Tier 2 targeted SRM and/or qRT-PCR. Notably, Leupaxin (LPXN) level was upregulated during Treg cell differentiation. Functional studies demonstrated that LPXN-deficient cells showed impaired expression of Treg protein markers FOXP3, IKZF4 and IKZF3 and impaired suppression of effector T cells. In addition, we identified a distinct CD160⁺ iTreg subpopulation characterized by a distinct proteomic signature as compared to CD160^– iTreg. Together, these findings provide a high-resolution proteomic landscape of human iTreg and identified a novel role of LPXN in the development and suppressive activity of iTreg.

PMID:42624209 | DOI:10.1016/j.mcpro.2026.101644