Soluble γc cytokine receptor suppresses IL-15 signaling and impairs iNKT cell development in the thymus

The soluble γc protein (sγc) is a naturally occurring splice isoform of the γc cytokine receptor that is produced by activated T cells and inhibits γc cytokine signaling. Here we show that sγc expression is also highly upregulated in immature CD4 + CD8 + thymocytes but then downregulated in mature thymocytes. These results indicate a developmentally controlled mechanism for sγc expression and suggest a potential role for sγc in regulating T cell development in the thymus. Indeed, sγc overexpression resulted in significantly reduced thymocyte numbers and diminished expansion of immature thymocytes, concordant to its role in suppressing signaling by IL-7, a critical γc cytokine in early thymopoiesis. Notably, sγc overexpression also impaired generation of i NKT cells, resulting in reduced i NKT cell percentages and numbers in the thymus. i NKT cell development requires IL-15, and we found that sγc interfered with IL-15 signaling to suppress i NKT cell generation in the thymus. Thus, sγc represents a new mechanism to control cytokine availability during T cell development that constrains mature T cell production and specifically i NKT cell generation in the thymus.