Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon

A Rivollier, J He, A Kole, V Valatas… - Journal of Experimental …, 2012 - rupress.org
Journal of Experimental Medicine, 2012rupress.org
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 …
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+CX3CR1CD11b DCs, CD103+CX3CR1CD11b+ DCs, and CD103CX3CR1intCD11b+ 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 CD103CX3CR1intCD11b+ 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.
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