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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

Authors :
Bernardo, D.
Marin, A.
Fernández-Tomé, S.
Montalban-Arques, A.
Carrasco, A.
Tristán, E.
Ortega-Moreno, L.
Mora-Gutiérrez, I.
Díaz-Guerra, A.
Caminero-Fernández, R.
Miranda, P.
Casals, F.
Caldas, M.
Jiménez, M.
Casabona, S.
Morena, F.
Esteve, M.
Santander, C.
Chaparro, M.
Gisbert, J.
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