Advanced

Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors

Bain, C. C.; Scott, C. L.; Uronen-Hansson, Heli LU ; Gudjonsson, Sigurdur LU ; Jansson, O.; Grip, Olof LU ; Guilliams, M.; Malissen, B.; Agace, W. W. and Mowat, A. Mc I. (2013) In Mucosal Immunology 6(3). p.498-510
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Mucosal Immunology
volume
6
issue
3
pages
498 - 510
publisher
Nature Publishing Group
external identifiers
  • wos:000317722800007
  • scopus:84876349699
ISSN
1933-0219
DOI
10.1038/mi.2012.89
language
English
LU publication?
yes
id
e63015f9-c312-48ff-845a-a7459cc47d81 (old id 3739006)
date added to LUP
2013-06-03 08:31:52
date last changed
2019-09-15 03:10:46
@article{e63015f9-c312-48ff-845a-a7459cc47d81,
  abstract     = {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.},
  author       = {Bain, C. C. and Scott, C. L. and Uronen-Hansson, Heli and Gudjonsson, Sigurdur and Jansson, O. and Grip, Olof and Guilliams, M. and Malissen, B. and Agace, W. W. and Mowat, A. Mc I.},
  issn         = {1933-0219},
  language     = {eng},
  number       = {3},
  pages        = {498--510},
  publisher    = {Nature Publishing Group},
  series       = {Mucosal Immunology},
  title        = {Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors},
  url          = {http://dx.doi.org/10.1038/mi.2012.89},
  volume       = {6},
  year         = {2013},
}