title: CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditions.
abstract: Intestinal mononuclear phagocytes (iMNP) are critically involved in mucosal immunity and tissue homeostasis. Two major non-overlapping populations of iMNP have been identified in mice. CD103(+) iMNP represent a migratory population capable of inducing tolerogenic responses, whereas CX3CR1(+) iMNP are resident cells with disease-promoting potential. CX3CR1(+) iMNP can further be subdivided based on differential expression of CX3CR1. Using CX3CR1(GFP/+) ×RAG2(-/-) mice, we demonstrate that CX3CR1(hi) and CX3CR1(lo) iMNP clearly differ with respect to their morphological and functional properties. Compared with CX3CR1(hi) iMNP, CX3CR1(lo) iMNP are polarised towards pro-inflammatory responses already under homeostatic conditions. During a CD4(+) T-cell-induced colitis, CX3CR1(lo) cells accumulate in the inflamed mucosa and upregulate the expression of pro-inflammatory cytokines and triggering receptor expressed on myeloid cells-1 (TREM-1). In contrast, CX3CR1(hi) iMNP retain their non-inflammatory profile even during intestinal inflammation. These findings identify two functionally distinct iMNP subsets based on differential expression of CX3CR1 and indicate an unanticipated stability of iMNP.
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Weber
authors.forename: Leslie
authors.initials: L
authors.lastname: Saurer
authors.forename: Mirjam
authors.initials: M
authors.lastname: Schenk
authors.forename: Nina
authors.initials: N
authors.lastname: Dickgreber
authors.forename: Christoph
authors.initials: C
authors.lastname: Mueller
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D003092:Colitis / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D020869:Gene Expression Profiling; D006706:Homeostasis; D018928:Immunity, Mucosal; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010586:Phagocytes / Q000145:classification* / Q000276:immunology*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; C499308:Rag2 protein, mouse; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1