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Human intestinal pro-inflammatory CD11chighCCR2+CX3CR1+macrophages, but not their tolerogenic CD11c−CCR2−CX3CR1−counterparts, are expanded in inflammatory bowel disease
Human intestinal pro-inflammatory CD11chighCCR2+CX3CR1+macrophages, but not their tolerogenic CD11c−CCR2−CX3CR1−counterparts, are expanded in inflammatory bowel disease
- Source :
- Mucosal Immunology; July 2018, Vol. 11 Issue: 4 p1114-1126, 13p
- Publication Year :
- 2018
-
Abstract
- Although macrophages (Mϕ) maintain intestinal immune homoeostasis, there is not much available information about their subset composition, phenotype and function in the human setting. Human intestinal Mϕ (CD45+HLA-DR+CD14+CD64+) can be divided into subsets based on the expression of CD11c, CCR2 and CX3CR1. Monocyte-like cells can be identified as CD11chighCCR2+CX3CR1+cells, a phenotype also shared by circulating CD14+monocytes. On the contrary, their Mϕ-like tissue-resident counterparts display a CD11c−CCR2−CX3CR1−phenotype. CD11chighmonocyte-like cells produced IL-1β, both in resting conditions and after LPS stimulation, while CD11c−Mϕ-like cells produced IL-10. CD11chighpro-inflammatory monocyte-like cells, but not the others, were increased in the inflamed colon from patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Tolerogenic IL-10-producing CD11c−Mϕ-like cells were generated from monocytes following mucosal conditioning. Finally, the colonic mucosa recruited circulating CD14+monocytes in a CCR2-dependent manner, being such capacity expanded in IBD. Mϕ subsets represent, therefore, transition stages from newly arrived pro-inflammatory monocyte-like cells (CD11chighCCR2+CX3CR1+) into tolerogenic tissue-resident (CD11c−CCR2−CX3CR1−) Mϕ-like cells as reflected by the mucosal capacity to recruit circulating monocytes and induce CD11c−Mϕ. The process is nevertheless dysregulated in IBD, where there is an increased migration and accumulation of pro-inflammatory CD11chighmonocyte-like cells.
Details
- Language :
- English
- ISSN :
- 19330219 and 19353456
- Volume :
- 11
- Issue :
- 4
- Database :
- Supplemental Index
- Journal :
- Mucosal Immunology
- Publication Type :
- Periodical
- Accession number :
- ejs49991082
- Full Text :
- https://doi.org/10.1038/s41385-018-0030-7