Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C hi monocyte precursors

C. C. Bain, C. L. Scott, H. Uronen-Hansson, S. Gudjonsson, O. Jansson, O. Grip, M. Guilliams, B. Malissen, W. W. Agace, A. Mc I. Mowat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

484 Citations (Scopus)

Abstract

Macrophages (mφ) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete mφ populations carry out these distinct functions or if resident mφ change during inflammation. We show here that most resident mφ in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCIIhi, but are resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10 constitutively, and express CD163 and CD206. A smaller population of CX3CR1int cells is present in resting colon and it expands during experimental colitis. Ly6ChiCCR2+ monocytes can give rise to all mφ 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 CX3CR1hi mφ. This process is arrested during experimental colitis, resulting in the accumulation of TLR-responsive pro-inflammatory mφ. Phenotypic analysis of human intestinal mφ indicates that analogous processes occur in the normal and Crohn's disease ileum. These studies show for the first time that resident and inflammatory mφ in the intestine represent alternative differentiation outcomes of the same precursor and targeting these events could offer routes for therapeutic intervention in IBD.

Original languageEnglish
Pages (from-to)498-510
Number of pages13
JournalMucosal Immunology
Volume6
Issue number3
DOIs
Publication statusPublished - May 2013

Bibliographical note

Funding Information:
We would like to thank Drs B. Jeppson, J. Marsal, U. H å kansson, G. Baseckas, and O. Patchan (Sk å ne University Hospital, Lund / Malm ö , Sweden) for collecting human ileum. The authors are grateful to Drs Oliver Pabst and Vuk Cerovic for constructive review of the manuscript. CCB, CLS, and AMcIM were supported by the Wellcome Trust and MRC UK.

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