CD45 regulates GM-CSF, retinoic acid and T-cell homing in intestinal inflammation
2016
CD45 is a leukocyte-specific tyrosine phosphatase important for T-cell development, and as a result, CD45(-/-) mice have substantially reduced numbers of T cells. Here we show that, upon dextran sodium sulfate (DSS)-induced colitis, CD45(-/-) mice have equivalent intestinal pathology and T-cell numbers in their colon as C57BL/6 mice and show enhanced weight loss. CD45(-/-) mice have a greater percentage of α4β7(+) T cells prior to and after colitis and an increased percentage of T cells producing inflammatory cytokines in the inflamed colon, suggesting that CD45(-/-) effector T cells preferentially home to the intestine. In DSS-induced colitis in CD45RAG(-/-) mice lacking an adaptive immune system, CD45 was required for optimal granulocyte-macrophage colony-stimulating factor (GM-CSF) and retinoic acid (RA) production by innate immune cells. Addition of CD45(+/+) T cells led to greater weight loss in the RAG(-/-) mice compared with CD45RAG(-/-) mice that correlated with reduced α4β7(+) T cells and lower recruitment to the colon of CD45RAG(-/-) mice in DSS-induced colitis. Addition of exogenous GM-CSF to CD45RAG(-/-) mice rescued RA production, increased colonic T-cell numbers, and increased weight loss. This demonstrates opposing effects of CD45 in innate and adaptive immune cells in proinflammatory responses and the expression of the gut-homing molecule, α4β7.
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