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

Abstract

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.

Commensal gut flora reduces susceptibility to experimentally induced colitis via T-cell-derived interleukin-101

“…10 We recently demonstrated that IL-10 acting via the IL-10R on macrophages/ monocytes and/or neutrophils inhibits the proinflammatory immune response in the model of LPS endotoxemia. 33 In order to determine the influence of the intestinal flora in this model, we exposed germfree WT and IL-10 À/À mice to DSS. Surprisingly, both germfree WT as well as IL-10 À/À mice were even more susceptible to DSS-induced colitis than SPF IL-10 À/À mice ( Fig.…”

Innate Transcriptional Networks Activated in Bladder in Response to Uropathogenic Escherichia coli Drive Diverse Biological Pathways and Rapid Synthesis of IL-10 for Defense against Bacterial Urinary Tract Infection

“…Plasma IL-10 was also elevated in patients with UPEC urosepsis (n = 57) compared with controls (n = 60) (B) (p = 0.001, unpaired Student t test, independent samples) illustrating IL-10 in the human immune response to UPEC. mechanism of immune regulation at the bladder-bacterial interface given the key role of IL-10R-dependent signaling in innate immunity (84). IL-10R is present on the surface of a variety of other human lymphoid and myeloid cells (85) and is upregulated during infection-induced inflammatory conditions such as sepsis (86).…”

Control of inflammation by stromal Hedgehog pathway activation restrains colitis

“…3A), SAG21k induction of IL-10 was even more dramatic in Gli1 + colon stromal cells (Fig. 3E), and this induction was not observed in FACS-isolated hematopoietic or epithelial cell populations from the colons of DSSexposed animals ( The antiinflammatory role of the IL-10 cytokine in IBD has long been known, with inactivating mutations in IL-10 or its receptor causally linked to IBD in humans and mice (1,2,(19)(20)(21). To determine whether IL-10 expression indeed mediates the protective effect of Hh stromal response, we exposed IL-10 mutant mice (IL-10 −/− ) to DSS and treated with SAG21k.…”