Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6Chi monocyte precursors
Autor: | Heli Uronen-Hansson, Calum C. Bain, O. Jansson, Martin Guilliams, Charlotte L. Scott, A. Mc I. Mowat, Sigurdur Gudjonsson, Olof Grip, William W. Agace, Bernard Malissen |
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Rok vydání: | 2013 |
Předmět: |
HOMEOSTASIS
SUBSETS Inflammatory bowel disease Monocytes ACTIVATION Mice 0302 clinical medicine Cell Movement Medicine and Health Sciences PROGRAM Antigens Ly Immunology and Allergy MACROPHAGES Cells Cultured Mice Knockout 0303 health sciences education.field_of_study Cell Differentiation Colitis Interleukin-10 Interleukin 10 medicine.anatomical_structure INTESTINAL MACROPHAGES CHEMOKINE RECEPTOR IL-10 Receptors Chemokine medicine.symptom ANTIINFLAMMATORY EXPRESSION Colon Receptors CCR2 Immunology Population CX3C Chemokine Receptor 1 Inflammation Context (language use) Biology Article 03 medical and health sciences medicine Animals Humans education Cell Proliferation 030304 developmental biology Macrophages Monocyte Histocompatibility Antigens Class II Biology and Life Sciences Inflammatory Bowel Diseases medicine.disease Mice Inbred C57BL CONVENTIONAL DENDRITIC CELLS CD163 030215 immunology |
Zdroj: | Mucosal Immunology Mucosal Immunology; Vol 6 MUCOSAL IMMUNOLOGY |
ISSN: | 1933-0219 |
Popis: | Macrophages (m phi) are essential for intestinal homeostasis and the pathology of inflammatory bowel disease (IBD), but it is unclear whether discrete m phi populations carry out these distinct functions or if resident m phi change during inflammation. We show here that most resident m phi in resting mouse colon express very high levels of CX3CR1, are avidly phagocytic and MHCII hi, but are resistant to Toll-like receptor (TLR) stimulation, produce interleukin 10 constitutively, and express CD163 and CD206. A smaller population of CX3CR1(int) cells is present in resting colon and it expands during experimental colitis. Ly6C(hi) CCR2(+) monocytes can give rise to all m phi subsets in both healthy and inflamed colon and we show that the CX3CR1int pool represents a continuum in which newly arrived, recently divided monocytes develop into resident CX3CR1 hi m phi. This process is arrested during experimental colitis, resulting in the accumulation of TLR-responsive pro-inflammatory m phi. Phenotypic analysis of human intestinal m phi indicates that analogous processes occur in the normal and Crohn's disease ileum. These studies show for the first time that resident and inflammatory m phi in the intestine represent alternative differentiation outcomes of the same precursor and targeting these events could offer routes for therapeutic intervention in IBD. |
Databáze: | OpenAIRE |
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