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
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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