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

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Intestinal immunity relies on diverse mononuclear phagocyte subsets.
• The small and large intestines have unique anatomical and immunological characteristics.
• It remains unclear if these differences necessitate organ-specific immune cell populations.

Purpose of the Study:

• To identify and characterize organ-specific mononuclear phagocyte subsets in the murine intestine.
• To investigate the functional roles of novel colon-specific immune cells in intestinal immunity.

Main Methods:

• A new strategy was employed to subset murine intestinal mononuclear phagocytes.
• Flow cytometry and transcriptional factor analysis (IRF4) were used to identify and characterize cell subsets.
• Functional assays were performed to assess the role of novel subsets in T-helper 17 (Th17) immunity.

Main Results:

• Two novel colon-specific subsets were identified: a macrophage subset and a Th17-inducing dendritic cell (DC) subset.
• These colon-specific cells co-expressed CD24 and CD14 and were dependent on the transcription factor IRF4.
• Novel IRF4-dependent CD14+CD24+ macrophages showed distinct marker expression and low IL-10 production compared to other intestinal macrophages.
• Colon-specific mononuclear phagocytes were essential for Th17 immunity in the colon.

Conclusions:

• The colon harbors unique mononuclear phagocyte populations distinct from those in the small intestine.
• These colon-specific cells, particularly IRF4-dependent CD14+CD24+ macrophages and DCs, play critical roles in Th17 immunity.
• There are distinct antigen-presenting cell requirements for Th17 immunity between the colon and small intestine.
• This study reveals unappreciated organ-specific diversity within intestinal mononuclear phagocytes.