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

• Published in: European journal of immunology Vol. 40; no. 2; pp. 443 - 448
• Main Authors: Pils, Marina C, Pisano, Fabio, Fasnacht, Nicolas, Heinrich, Jan-Michael, Groebe, Lothar, Schippers, Angela, Rozell, Björn, Jack, Robert S, Müller, Werner
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.02.2010; WILEY‐VCH Verlag
• Subjects: Animals; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cecum - parasitology; Cecum - pathology; Conditional gene targeting; Endotoxemia - chemically induced; Endotoxemia - immunology; Endotoxemia - metabolism; Female; IL‐10 receptor; Immune regulation; Interleukin-10 - genetics; Interleukin-10 - immunology; Interleukin-10 - metabolism; Lipopolysaccharide; Lipopolysaccharides; Macrophages - immunology; Macrophages - metabolism; Male; Medicin och hälsovetenskap; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Monocytes - immunology; Monocytes - metabolism; Neutrophils - immunology; Neutrophils - metabolism; Receptors, Interleukin-10 - genetics; Receptors, Interleukin-10 - immunology; Receptors, Interleukin-10 - metabolism; Signal Transduction - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Th1 Cells - immunology; Th1 Cells - metabolism; Trichuriasis - immunology; Trichuriasis - parasitology; Trichuris - growth & development; Trichuris - immunology; Trichuris muris
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.200939592

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.