Regulation of γδ T cell effector fate specification by ribosomal protein paralogs (HEM3P.285)

Abstract

Abstract γδ T cells are key mediators of inflammation that play a crucial role in preserving epithelial barriers and eradicating cutaneous tumors. The molecular mechanisms that control γδ T cell development and function, however, remain poorly understood. We have previously reported that the ribosomal protein paralogs Rpl22 and Rpl22l1 have antagonistic roles during hematopoietic stem cell emergence. Consequently, we sought to determine if Rpl22 and Rpl22l1 might play roles in more differentiated hematopoietic lineages. We have now demonstrated that γδ T cell development is not arrested in the absence of Rpl22 or Rpl22l1, suggesting these proteins are dispensable γδ T cell development; however, Rpl22 and Rpl22l1 do appear to regulate the specification of γδ effector fate during development in the thymus and have opposing roles in this process. Specifically, Rpl22-deficiency enhances the generation of IL-17-producing γδ T cells. In contrast, Rpl22l1-deficiency leads to an expansion of IFN-γ-producing γδ T cells and, in particular, the Vγ1.1+ innate-like γδ T cell subset. Rpl22 and Rpl22l1 are RNA-binding proteins that exert their control over developmental processes extraribosomally (i.e., away from the ribosome) by binding and regulating the expression of cellular RNA targets. Our efforts to identify the key cellular RNAs through which Rpl22 and Rpl22l1 influence γδ T cell effector fate will be presented.