TY - JOUR
T1 - Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization
AU - Denning, Timothy L.
AU - Norris, Brian A.
AU - Medina-Contreras, Oscar
AU - Manicassamy, Santhakumar
AU - Geem, Duke
AU - Madan, Rajat
AU - Karp, Christopher L.
AU - Pulendran, Bali
PY - 2011/7/15
Y1 - 2011/7/15
N2 - Although several subsets of intestinal APCs have been described, there has been no systematic evaluation of their phenotypes, functions, and regional localization to date. In this article, we used 10-color flow cytometry to define the major APC subsets in the small and large intestine lamina propria. Lamina propria APCs could be subdivided into CD11c+CD11b-, CD11c+CD11b+, and CD11cdullCD11b+ subsets. CD11c+CD11b- cells were largely CD103 +F4/80- dendritic cells (DCs), whereas the CD11c + CD11b+ subset comprised CD11c+CD11b +CD103+F4/80- DCs and CD11c +CD11b+CD1032F4/80+ macrophage-like cells. The majority of CD11cdullCD11b+ cells were CD103 -F4/80+ macrophages. Although macrophages were more efficient at inducing Foxp3+ regulatory T (Treg) cells than DCs, at higher T cell/APC ratios, all of the DC subsets efficiently induced Foxp3+ Treg cells. In contrast, only CD11c +CD11b+CD103+ DCs efficiently induced Th17 cells. Consistent with this, the regional distribution of CD11c+ CD11b+CD103+ DCs correlated with that of Th17 cells, with duodenum > jejunum > ileum > colon. Conversely, CD11c +CD11b- CD103+ DCs, macrophages, and Foxp3 + Treg cells were most abundant in the colon and scarce in the duodenum. Importantly, however, the ability of DC and macrophage subsets to induce Foxp3+ Treg cells versus Th17 cells was strikingly dependent on the source of the mouse strain. Thus, DCs from C57BL/6 mice from Charles River Laboratories (that have segmented filamentous bacteria, which induce robust levels of Th17 cells in situ) were more efficient at inducing Th17 cells and less efficient at inducing Foxp3+ Treg cells than DCs from B6 mice from The Jackson Laboratory. Thus, the functional specializations of APC subsets in the intestine are dependent on the T cell/APC ratio, regional localization, and source of the mouse strain.
AB - Although several subsets of intestinal APCs have been described, there has been no systematic evaluation of their phenotypes, functions, and regional localization to date. In this article, we used 10-color flow cytometry to define the major APC subsets in the small and large intestine lamina propria. Lamina propria APCs could be subdivided into CD11c+CD11b-, CD11c+CD11b+, and CD11cdullCD11b+ subsets. CD11c+CD11b- cells were largely CD103 +F4/80- dendritic cells (DCs), whereas the CD11c + CD11b+ subset comprised CD11c+CD11b +CD103+F4/80- DCs and CD11c +CD11b+CD1032F4/80+ macrophage-like cells. The majority of CD11cdullCD11b+ cells were CD103 -F4/80+ macrophages. Although macrophages were more efficient at inducing Foxp3+ regulatory T (Treg) cells than DCs, at higher T cell/APC ratios, all of the DC subsets efficiently induced Foxp3+ Treg cells. In contrast, only CD11c +CD11b+CD103+ DCs efficiently induced Th17 cells. Consistent with this, the regional distribution of CD11c+ CD11b+CD103+ DCs correlated with that of Th17 cells, with duodenum > jejunum > ileum > colon. Conversely, CD11c +CD11b- CD103+ DCs, macrophages, and Foxp3 + Treg cells were most abundant in the colon and scarce in the duodenum. Importantly, however, the ability of DC and macrophage subsets to induce Foxp3+ Treg cells versus Th17 cells was strikingly dependent on the source of the mouse strain. Thus, DCs from C57BL/6 mice from Charles River Laboratories (that have segmented filamentous bacteria, which induce robust levels of Th17 cells in situ) were more efficient at inducing Th17 cells and less efficient at inducing Foxp3+ Treg cells than DCs from B6 mice from The Jackson Laboratory. Thus, the functional specializations of APC subsets in the intestine are dependent on the T cell/APC ratio, regional localization, and source of the mouse strain.
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U2 - 10.4049/jimmunol.1002701
DO - 10.4049/jimmunol.1002701
M3 - Article
C2 - 21666057
AN - SCOPUS:79960513242
SN - 0022-1767
VL - 187
SP - 733
EP - 747
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -