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A role for transcriptional regulator Id2 in natural killer T cells


Natural Killer T (NKT) cells are a critical component of the body's immune system and function to activate both innate and adaptive immune cells. NKT cells are T lymphocyte lineage cells that develop in the thymus and express a variety of both NK and T cell surface markers. Mice deficient in the inhibitor of DNA binding protein-2 (Id2) fail to develop natural killer cells, CD8[alpha]⁺ dendritic cells, [alpha][beta] IELs, Langerhans cells, and lack lymph nodes. Absence of Id2 also affects the CD8⁺ T cell immune response to infection, resulting in reduced survival of effector CD8⁺ T cells and impaired memory formation. The role of Id2 in NKT cell physiology has not been addressed. Here, I show that bone marrow chimeras reconstituted with Id2-deficient hematopoietic stem cells have fewer NKT cells in the liver, spleen, thymus, and bone marrow compared to chimeras generated with Id2- sufficient HSCs, with the most severe defect (10-fold reduction) occurring in the liver. Despite their diminished numbers, Id2-deficient NKT cells produce cytokines after activation with [alpha]- galactocsylceramide, suggesting normal functional activity, and have similar expression levels of multiple maturation markers compared to Id2-suficient chimeras. However, Id2- deficient NKT cells have lower mRNA and cell surface expression of the chemokine receptor CXCR6, which is thought to have a critical role in NKT cell accumulation in the liver. The NKT cell defect in Id2-deficient chimeras is not due to an inability of cells to migrate to the peripheral tissues, but could be the result of increased cell death. Early NKT cell development is not affected by Id2 deficiency, possibly due to compensation by Id3, but maturation in the periphery is impaired. These experiments point to a role for Id2 in regulating a CXCR6- mediated survival/maturation signal essential for accumulation of NKT cells in the liver

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