Journal Article

CCR2 promotes monocyte recruitment and intestinal inflammation in mice lacking the interleukin-10 receptor

Glickman, Jonathan N., Abd El Wahab, Ashraf M., Horwitz, Bruce H., Snapper, Scott B., El Naenaeey, El Sayed Y., Elmowalid, Gamal A., Karagiannis, Konstantinos, Redhu, Naresh S., Patik, Izabel, El Sayed, Shorouk

2022

Overview

Macrophages are a heterogeneous population of mononuclear phagocytes abundantly distributed throughout the intestinal compartments that adapt to microenvironmental specific cues. In adult mice, the majority of intestinal macrophages exhibit a mature phenotype and are derived from blood monocytes. In the steady-state, replenishment of these cells is reduced in the absence of the chemokine receptor CCR2. Within the intestine of mice with colitis, there is a marked increase in the accumulation of immature macrophages that demonstrate an inflammatory phenotype. Here, we asked whether CCR2 is necessary for the development of colitis in mice lacking the receptor for IL10. We compared the development of intestinal inflammation in mice lacking IL10RA or both IL10RA and CCR2. The absence of CCR2 interfered with the accumulation of immature macrophages in IL10R-deficient mice, including a novel population of rounded submucosal Iba1 + cells, and reduced the severity of colitis in these mice. In contrast, the absence of CCR2 did not reduce the augmented inflammatory gene expression observed in mature intestinal macrophages isolated from mice lacking IL10RA. These data suggest that both newly recruited CCR2-dependent immature macrophages and CCR2-independent residual mature macrophages contribute to the development of intestinal inflammation observed in IL10R-deficient mice.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250/127/1213 / 631/250/2504/342 / 631/250/256 / 692/4020/1503/257 / Animals / CC chemokine receptors / CCR2 protein / Chemokine receptors / Colitis / Colitis - genetics / Colitis - immunology / Female / Gene expression / Humanities and Social Sciences / Humans / Inflammation / Inflammatory bowel disease / Interleukin 1 / Interleukin 10 / Interleukin 10 receptors / Interleukin-10 Receptor alpha Subunit - genetics / Interleukin-10 Receptor alpha Subunit - immunology / Intestine / Intestines - immunology / Leukocytes (mononuclear) / Macrophages / Macrophages - immunology / Male / Mice / Mice, Knockout / Monocyte chemoattractant protein 1 / Monocytes / Monocytes - immunology / multidisciplinary / Phagocytes / Phenotypes / Receptors, CCR2 - genetics / Receptors, CCR2 - immunology / Science / Science (multidisciplinary)