PMID- 22231304 OWN - NLM STAT- MEDLINE DCOM- 20120409 LR - 20220317 IS - 1540-9538 (Electronic) IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 209 IP - 1 DP - 2012 Jan 16 TI - Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. PG - 139-55 LID - 10.1084/jem.20101387 [doi] AB - Dendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80(hi)CX3CR1(hi) (CD11b(+)CD103(-)) cells account for 80% of mouse colonic lamina propria MHC-II(hi) cells. Both CD11c(+) and CD11c(-) cells within this population were identified as MPs based on multiple criteria, including an MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs based on phenotypic and functional analysis and comprise three separate CD11c(hi) cell populations: CD103(+)CX3CR1(-)CD11b(-) DCs, CD103(+)CX3CR1(-)CD11b(+) DCs, and CD103(-)CX3CR1(int)CD11b(+) DCs. In noninflammatory conditions, Ly6C(hi) monocytes (MOs) differentiated primarily into CD11c(+) but not CD11c(-) MPs. In contrast, during colitis, Ly6C(hi) MOs massively invaded the colon and differentiated into proinflammatory CD103(-)CX3CR1(int)CD11b(+) DCs, which produced high levels of IL-12, IL-23, iNOS, and TNF. These findings demonstrate the dual capacity of Ly6C(hi) blood MOs to differentiate into either regulatory MPs or inflammatory DCs in the colon and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions. FAU - Rivollier, Aymeric AU - Rivollier A AD - Mucosal Immunobiology Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. FAU - He, Jianping AU - He J FAU - Kole, Abhisake AU - Kole A FAU - Valatas, Vassilis AU - Valatas V FAU - Kelsall, Brian L AU - Kelsall BL LA - eng GR - T32 GM008169/GM/NIGMS NIH HHS/United States GR - ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20120109 PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (Antigens, CD) RN - 0 (Antigens, Ly) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Integrin alpha Chains) RN - 0 (Lipopolysaccharides) RN - 0 (Ly-6C antigen, mouse) RN - 0 (alpha E integrins) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.7.7.- (Transposases) SB - IM MH - Adoptive Transfer MH - Animals MH - Antigens, CD/genetics MH - Antigens, Ly/analysis MH - Cell Differentiation/*immunology MH - Colon/*immunology/metabolism MH - Cytokines/biosynthesis/immunology MH - Dendritic Cells/cytology/*immunology MH - Inflammation/*immunology/metabolism MH - Inflammation Mediators/immunology/metabolism MH - Integrin alpha Chains/deficiency/genetics MH - Interferon-gamma/biosynthesis MH - Interleukin-10/biosynthesis/immunology MH - Lipopolysaccharides/immunology MH - Macrophages/cytology/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Monocytes/*cytology MH - Mucous Membrane/immunology/metabolism MH - T-Lymphocytes/immunology/metabolism MH - Transposases/genetics PMC - PMC3260867 EDAT- 2012/01/11 06:00 MHDA- 2012/04/10 06:00 PMCR- 2012/07/16 CRDT- 2012/01/11 06:00 PHST- 2012/01/11 06:00 [entrez] PHST- 2012/01/11 06:00 [pubmed] PHST- 2012/04/10 06:00 [medline] PHST- 2012/07/16 00:00 [pmc-release] AID - jem.20101387 [pii] AID - 20101387 [pii] AID - 10.1084/jem.20101387 [doi] PST - ppublish SO - J Exp Med. 2012 Jan 16;209(1):139-55. doi: 10.1084/jem.20101387. Epub 2012 Jan 9.