The Timing and Abundance of IL-2Rβ (CD122) Expression Control Thymic iNKT Cell Generation and NKT1 Subset Differentiation
Hee Yeun Won, Hye Kyung Kim, Assiatu Crossman, Parirokh Awasthi, Ronald E. Gress, Jung‐Hyun Park
Abstract
Invariant NKT ( i NKT) cells are thymus-generated innate-like T cells, comprised of three distinct subsets with divergent effector functions. The molecular mechanism that drives the lineage trifurcation of immature i NKT cells into the NKT1, NKT2, and NKT17 subsets remains a controversial issue that remains to be resolved. Because cytokine receptor signaling is necessary for i NKT cell generation, cytokines are proposed to contribute to i NKT subset differentiation also. However, the precise roles and requirements of cytokines in these processes are not fully understood. Here, we show that IL-2Rβ, a nonredundant component of the IL-15 receptor complex, plays a critical role in both the development and differentiation of thymic i NKT cells. While the induction of IL-2Rβ expression on postselection thymocytes is necessary to drive the generation of i NKT cells, surprisingly, premature IL-2Rβ expression on immature i NKT cells was detrimental to their development. Moreover, while IL-2Rβ is necessary for NKT1 generation, paradoxically, we found that the increased abundance of IL-2Rβ suppressed NKT1 generation without affecting NKT2 and NKT17 cell differentiation. Thus, the timing and abundance of IL-2Rβ expression control i NKT lineage fate and development, thereby establishing cytokine receptor expression as a critical regulator of thymic i NKT cell differentiation.