Cord-derived iNKT cells are enriched with human NKT10 and exert the immunosuppressive function through the interaction with NRP1 [scMultiomics-seq]

Invariant Natural Killer T (iNKT) cells are a unique subset of T lymphocytes that recognize glycolipid antigens presented by the non-polymorphic MHC class I-like molecule CD1d through a semi-invariant T cell antigen receptor. In mice, this receptor consists of the invariant Vα14Ja18 (TRAV11+TRAJ18+) chain paired with Vβ8, Vβ7, or Vβ2, while in humans, it comprises Vα24Ja18 (TRAV10+TRAJ18+) paired with Vβ11. Upon activation, iNKT cells modulate adaptive immunity by promoting either immune suppression or inflammation through the production of Th1- and Th2-type cytokines. They also enhance adaptive T and B cell responses via the CD40-CD40L feedback loop with antigen-presenting dendritic cells (DCs). iNKT cells exhibit phenotypic and functional heterogeneity, with subsets including CD4+ and CD4- populations, as well as functionally distinct NKT1 (Th1), NKT2 (Th2), NKT10 (Th10), and NKT17 (Th17) cells. The developmental pathways and immunological roles of murine iNKT cells are well characterized, highlighting their functional plasticity in immune modulation. The NKT10 subset, in particular, has been studied in various murine models and demonstrated a regulatory function within CD4+ iNKT cells. These cells are enriched in specific NKT10 signature markers, including IL-10, NRP1, and PD-1, which define their immunoregulatory properties. Despite these findings in mice, the phenotype and function of IL-10-producing human iNKT cells remain poorly characterized, and their regulatory role in human diseases is not well understood. Here, we aim to characterize human NKT10 cells derived from cord blood iNKT cells and explore their therapeutic potential in bone marrow transplantation.