Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors.

ABSTRACT: Macrophages (m?) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete m? populations carry out these distinct functions or if resident m? change during inflammation. We show here that most resident m? in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCII(hi), but are resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10 constitutively, and express CD163 and CD206. A smaller population of CX3CR1(int) cells is present in resting colon and it expands during experimental colitis. Ly6C(hi)CCR2(+) monocytes can give rise to all m? subsets in both healthy and inflamed colon and we show that the CX3CR1(int) pool represents a continuum in which newly arrived, recently divided monocytes develop into resident CX3CR1(hi) m?. This process is arrested during experimental colitis, resulting in the accumulation of TLR-responsive pro-inflammatory m?. Phenotypic analysis of human intestinal m? indicates that analogous processes occur in the normal and Crohn's disease ileum. These studies show for the first time that resident and inflammatory m? in the intestine represent alternative differentiation outcomes of the same precursor and targeting these events could offer routes for therapeutic intervention in IBD.

SUBMITTER: Bain CC 

PROVIDER: S-EPMC3629381 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature