Monocytes/macrophages and/or neutrophils are the target of IL‐10 in the LPS endotoxemia model

IL‐10 is a potent regulator of the innate and adaptive immune responses. Several cell types produce IL‐10 and its receptor chains and these may regulate different immune responses. Here we report that inactivation of the IL‐10 receptor (IL‐10R1) gene in mice leads to an increased susceptibility to chemically induced colitis as in the classical IL‐10‐deficient mutant. To identify the cells regulated by IL‐10 in immune responses, we generated several cell type specific IL‐10R1‐deficient mutants. We show that, in an IL‐10‐dependent LPS model of endotoxemia, dampening of the immune response requires expression of IL‐10R1 in monocytes/macrophages and/or neutrophils but not in T cells nor B cells. As the macrophage and/or neutrophil‐specific IL‐10‐deficient mutants also display the same phenotype, our results suggest that an autocrine loop in monocytes/macrophages is the most probable mechanism for the regulation of an LPS‐induced septic shock. In contrast, in an IL‐10‐regulated T‐cell response to Trichuris muris infection, IL‐10 acting on T cells or monocytes/macrophages/neutrophils is not critical for the control of the infection.

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