The serine/threonine kinase Pim1 permits development and homeostasis of CD4+ T lymphocytes in the absense of common gamma chain cytokine receptor signaling
Linowes, Brett A
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Signaling over the common gamma chain (γc) cytokine receptor is a critical and non-redundant requirement for the development of all lymphocytes. In both human and mice, absent γc cytokine signaling results in a complete block of all T lineage lymphocyte development, including αβ T cells and γδ T cells, NKT cells and TCRβ+CDSαα intraepithelial lymphocytes (IEL). The reasons for such γc cytokine requ irement are not completely understood and still debated. Among others, however, induction of the serine/threonine kinase Pim1 is a major downstream event as Pim1 provides survival and increased metabolic activity upon γc cytokine signaling. As such, here we asked whether Pim1 is sufficient to restore lymphocyte development in the absence of γc receptor expression. By analyzing γc-deficient mice that are expressing a transgenic Pim1, here we show that Pim-1 significantly restores αβ T cell development in the thymus and greatly improves peripheral homeostasis of mature T cells. Notably, such effects were largely restricted to CD4 linage T cells as CDS thymocytes and CDS+ T cells poorly responded to Pim1 overexpression. Moreover, transgenic Pim1 failed to restore any other T lymphocyte lineage cells than αβ T cells, as we still observed a complete lack of γδ T-, NKT-cells and TCRβ+CDSαα IELs in these mice. Thus, our current results unveil distinct requirements of γc downstream signaling between CD4+ αβ T cells and all other T lymphocyte lineage cells, and propose Pim-1 as a novel effector molecule, sufficient to drive CD4+ αβ T cell development and differentiation in the absence of γc cytokine signaling.
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