| 1. |
|
|
| 2. |
- Bain, C. C., et al.
(author)
-
Resident and pro-inflammatory macrophages in the colon represent alternative context-dependent fates of the same Ly6C(hi) monocyte precursors
- 2013
-
In: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 6:3, s. 498-510
-
Journal article (peer-reviewed)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.
|
|
| 3. |
- Scott, C L, et al.
(author)
-
CCR2(+)CD103(-) intestinal dendritic cells develop from DC-committed precursors and induce interleukin-17 production by T cells.
- 2015
-
In: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 8:2, s. 327-339
-
Journal article (peer-reviewed)abstract
- The identification of intestinal macrophages (mφs) and dendritic cells (DCs) is a matter of intense debate. Although CD103(+) mononuclear phagocytes (MPs) appear to be genuine DCs, the nature and origins of CD103(-) MPs remain controversial. We show here that intestinal CD103(-)CD11b(+) MPs can be separated clearly into DCs and mφs based on phenotype, gene profile, and kinetics. CD64(-)CD103(-)CD11b(+) MPs are classical DCs, being derived from Flt3 ligand-dependent, DC-committed precursors, not Ly6C(hi) monocytes. Surprisingly, a significant proportion of these CD103(-)CD11b(+) DCs express CCR2 and there is a selective decrease in CD103(-)CD11b(+) DCs in mice lacking this chemokine receptor. CCR2(+)CD103(-) DCs are present in both the murine and human intestine, drive interleukin (IL)-17a production by T cells in vitro, and show constitutive expression of IL-12/IL-23p40. These data highlight the heterogeneity of intestinal DCs and reveal a bona fide population of CCR2(+) DCs that is involved in priming mucosal T helper type 17 (Th17) responses.Mucosal Immunology advance online publication, 20 August 2014; doi:10.1038/mi.2014.70.
|
|
