Tbet promotes NK cell egress from the bone marrow and CXCR6 expression in immature NK cells

Abstract

<jats:p>Tbet-deficient mice have reduced NK cells in blood and spleen, but increased NK cells in bone marrow and lymph nodes, a phenotype that is thought to be due to defective migration. Here, we revisit the role of Tbet in NK cell bone marrow egress. We definitively show that the accumulation of NK cells in the bone marrow of Tbet-deficient (Tbx21<jats:sup>-/-</jats:sup>) animals occurs because of a cell-intrinsic migration defect. We identify a profile of gene expression, co-ordinated by Tbet, which affects the localisation of NK cells in the bone marrow. Tbet promotes Cxcr6 expression and immature NK cells accumulate in the bone marrow of CXCR6-deficient mice. This suggests that CXCR6 is among the mediators of migration, controlled by Tbet, that co-ordinate NK cell bone marrow egress.</jats:p>

Bone Marrow NK Cells: Origin, Distinctive Features, and Requirements for Tissue Localization

“…The role of CXCR6 in promoting BM colonization by these cells was not investigated, but a fraction of immature BM NK cells was found to express CXCR6 also in the mouse, and deletion of Cxcr6 gene limits the egress of this population into the blood circulation. Similarly to CXCR3 and S1PR5, expression of this chemokine receptor is regulated by the transcription factor TBET since it is suppressed in BM NK cells of TBET knockout mice (41, 42).…”