Affiliation:
1. Mucosal Immunobiology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Abstract
Dendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80hiCX3CR1hi (CD11b+CD103−) cells account for 80% of mouse colonic lamina propria MHC-IIhi cells. Both CD11c+ and CD11c− cells within this population were identified as MPs based on multiple criteria, including an MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs based on phenotypic and functional analysis and comprise three separate CD11chi cell populations: CD103+CX3CR1−CD11b− DCs, CD103+CX3CR1−CD11b+ DCs, and CD103−CX3CR1intCD11b+ DCs. In noninflammatory conditions, Ly6Chi monocytes (MOs) differentiated primarily into CD11c+ but not CD11c− MPs. In contrast, during colitis, Ly6Chi MOs massively invaded the colon and differentiated into proinflammatory CD103−CX3CR1intCD11b+ DCs, which produced high levels of IL-12, IL-23, iNOS, and TNF. These findings demonstrate the dual capacity of Ly6Chi blood MOs to differentiate into either regulatory MPs or inflammatory DCs in the colon and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions.
Publisher
Rockefeller University Press
Subject
Immunology,Immunology and Allergy
Cited by
455 articles.
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