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CX3CR1 defines functionally distinct intestinal mononuclear phagocyte subsets which maintain their respective functions during homeostatic and inflammatory conditions
Author(s) -
Weber Benjamin,
Saurer Leslie,
Schenk Mirjam,
Dickgreber Nina,
Mueller Christoph
Publication year - 2011
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201040965
Subject(s) - cx3cr1 , biology , immunology , mononuclear phagocyte system , inflammation , population , homeostasis , immune system , microbiology and biotechnology , chemokine , chemokine receptor , medicine , environmental health
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.