期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 42, 期 12, 页码 3150-3166出版社
WILEY-BLACKWELL
DOI: 10.1002/eji.201242847
关键词
CD64; Colitis; Dendritic cells; Intestine; MFs
类别
资金
- CNRS
- INSERM
- European Communities Framework Program 7 (MASTERSWITCH Integrating Project
- European Communities Framework Program 7 [HEALTH-F2-2008-223404]
- European Communities Framework Program 7 (NANOASIT Euronanomed Project)
- AFM
- FRM
- ANR (Skin DCs)
- Ministere de la Recherche
- European Communities [237109]
- Cancer Research UK
- Leukaemia and Lymphoma Research
- CNRS/INSERM ATIP/AVENIR program
- Medical Research Council
- Wellcome Trust (UK)
- Cancer Research UK [15689] Funding Source: researchfish
Dendritic cells (DCs) and monocyte-derived macrophages (MFs) are key components of intestinal immunity. However, the lack of surface markers differentiating MFs from DCs has hampered understanding of their respective functions. Here, we demonstrate that, using CD64 expression, MFs can be distinguished from DCs in the intestine of both mice and humans. On that basis, we revisit the phenotype of intestinal DCs in the absence of contaminating MFs and we delineate a developmental pathway in the healthy intestine that leads from newly extravasated Ly-6Chi monocytes to intestinal MFs. We determine how inflammation impacts this pathway and show that T cell-mediated colitis is associated with massive recruitment of monocytes to the intestine and the mesenteric lymph node (MLN). There, these monocytes differentiate into inflammatory MFs endowed with phagocytic activity and the ability to produce inducible nitric oxide synthase. In the MLNs, inflammatory MFs are located in the T-cell zone and trigger the induction of proinflammatory T cells. Finally, T cell-mediated colitis develops irrespective of intestinal DC migration, an unexpected finding supporting an important role for MLN-resident inflammatory MFs in the etiology of T cell-mediated colitis.
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