Th17 Immunity in the Colon Is Controlled by Two Novel Subsets of Colon-Specific Mononuclear Phagocytes

Abstract

Intestinal immunity is coordinated by specialized mononuclear phagocyte populations, constituted by a diversity of cell subsets. Although the cell subsets constituting the mononuclear phagocyte network are thought to be similar in both small and large intestine, these organs have distinct anatomy, microbial composition, and immunological demands. Whether these distinctions demand organ-specific mononuclear phagocyte populations with dedicated organ-specific roles in immunity are unknown. Here we implement a new strategy to subset murine intestinal mononuclear phagocytes and identify two novel subsets which are colon-specific: a macrophage subset and a Th17-inducing dendritic cell (DC) subset. Colon-specific DCs and macrophages co-expressed CD24 and CD14, and surprisingly, both were dependent on the transcription factor IRF4. Novel IRF4-dependent CD14+CD24+ macrophages were markedly distinct from conventional macrophages and failed to express classical markers including CX3CR1, CD64 and CD88, and surprisingly expressed little IL-10, which was otherwise robustly expressed by all other intestinal macrophages. We further found that colon-specific CD14+CD24+ mononuclear phagocytes were essential for Th17 immunity in the colon, and provide definitive evidence that colon and small intestine have distinct antigen presenting cell requirements for Th17 immunity. Our findings reveal unappreciated organ-specific diversity of intestine-resident mononuclear phagocytes and organ-specific requirements for Th17 immunity.

The intestinal immune system and gut barrier function in obesity and ageing

“…Furthermore, novel intestine‐resident mononuclear phagocytes were recently characterized in the colon. Indeed, subsets of IRF4‐dependent CD14 + CD24 + macrophages and DCs were found to be essential in Th17‐mediated intestinal immunity [27]. This study highlights the regional differences of immune cell populations.…”

Hemorrhagic Transformation in Patients with Large-Artery Atherosclerotic Stroke is Associated with Gut Microbiota and LPS-TLR4 Signaling Pathway

“…The antibiotics treatment was performed and controlled as previously report (39,40). To deplete gut ora, rats were given broad-spectrum antibiotics (vancomycin 0.5g/L, ampicillin 1g/L, metronidazole 1g/L, neomycin sulfate 1g/L; all from Meilun Biotechnology, Dalian, China) in drinking water for 4 weeks.…”

Abnormal Changes of Monocyte Subsets in Patients With Sjögren’s Syndrome

“…Mononuclear phagocytes (MNPs) are the most common innate immune cells with key roles in both immunity and autoimmunity (8)(9)(10)(11). MNPs in blood are mainly composed of monocytes and dendritic cells (DCs), both of which have heterogenerous subsets with distinct phenotypes (12,13).…”