First Author | Luo S | Year | 2021 |
Journal | JCI Insight | Volume | 6 |
Issue | 18 | PubMed ID | 34549726 |
Mgi Jnum | J:330518 | Mgi Id | MGI:6787439 |
Doi | 10.1172/jci.insight.148038 | Citation | Luo S, et al. (2021) CD138 expression is a molecular signature but not a developmental requirement for RORgammat+ NKT17 cells. JCI Insight 6(18):e148038 |
abstractText | Invariant NKT (iNKT) cells are potent immunomodulatory cells that acquire effector function during their development in the thymus. IL-17-producing iNKT cells are commonly referred to as NKT17 cells, and they are unique among iNKT cells to express the heparan sulfate proteoglycan CD138 and the transcription factor RORgammat. Whether and how CD138 and RORgammat contribute to NKT17 cell differentiation, and whether there is an interplay between RORgammat and CD138 expression to control iNKT lineage fate, remain mostly unknown. Here, we showed that CD138 expression was only associated with and not required for the differentiation and IL-17 production of NKT17 cells. Consequently, CD138-deficient mice still generated robust numbers of IL-17-producing RORgammat+ NKT17 cells. Moreover, forced expression of RORgammat significantly promoted the generation of thymic NKT17 cells, but did not induce CD138 expression on non-NKT17 cells. These results indicated that NKT17 cell generation and IL-17 production were driven by RORgammat, employing mechanisms that were independent of CD138. Therefore, our study effectively dissociated CD138 expression from the RORgammat-driven molecular pathway of NKT17 cell differentiation. |