TY - JOUR
T1 - Specific microbiota-induced intestinal Th17 differentiation requires MHC class II but not GALT and mesenteric lymph nodes
AU - Geem, Duke
AU - Medina-Contreras, Oscar
AU - McBride, Michelle
AU - Newberry, Rodney D.
AU - Koni, Pandelakis A.
AU - Denning, Timothy L.
PY - 2014/7/1
Y1 - 2014/7/1
N2 - IL-17-expressing CD4+ T lymphocytes (Th17 cells) naturally reside in the intestine where specific cytokines and microbiota, such as segmented filamentous bacteria (SFB), promote their differentiation. Intestinal Th17 cells are thought to initially differentiate in the GALT and/or mesenteric lymph nodes upon Ag encounter and subsequently home to the lamina propria (LP) where they mediate effector functions. However, whether GALTand/or mesenteric lymph nodes are required for intestinal Th17 differentiation as well as how microbiota containing SFB regulate Ag-specific intestinal Th17 cells remain poorly defined. In this study, we observed that naive CD4+ T cells were abundant in the intestinal LP prior to weaning and that the accumulation of Th17 cells in response to microbiota containing SFB occurred in the absence of lymphotoxin-dependent lymphoid structures and the spleen. Furthermore, the differentiation of intestinal Th17 cells in the presence of microbiota containing SFB was dependent on MHC class II expression by CD11c+ cells. Lastly, the differentiation of Ag-specific Th17 cells required both the presence of cognate Ag and microbiota containing SFB. These findings suggest that microbiota containing SFB create an intestinal milieu that may induce Ag-specific Th17 differentiation against food and/or bacterial Ags directly in the intestinal LP.
AB - IL-17-expressing CD4+ T lymphocytes (Th17 cells) naturally reside in the intestine where specific cytokines and microbiota, such as segmented filamentous bacteria (SFB), promote their differentiation. Intestinal Th17 cells are thought to initially differentiate in the GALT and/or mesenteric lymph nodes upon Ag encounter and subsequently home to the lamina propria (LP) where they mediate effector functions. However, whether GALTand/or mesenteric lymph nodes are required for intestinal Th17 differentiation as well as how microbiota containing SFB regulate Ag-specific intestinal Th17 cells remain poorly defined. In this study, we observed that naive CD4+ T cells were abundant in the intestinal LP prior to weaning and that the accumulation of Th17 cells in response to microbiota containing SFB occurred in the absence of lymphotoxin-dependent lymphoid structures and the spleen. Furthermore, the differentiation of intestinal Th17 cells in the presence of microbiota containing SFB was dependent on MHC class II expression by CD11c+ cells. Lastly, the differentiation of Ag-specific Th17 cells required both the presence of cognate Ag and microbiota containing SFB. These findings suggest that microbiota containing SFB create an intestinal milieu that may induce Ag-specific Th17 differentiation against food and/or bacterial Ags directly in the intestinal LP.
UR - http://www.scopus.com/inward/record.url?scp=84903629396&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1303167
DO - 10.4049/jimmunol.1303167
M3 - Article
C2 - 24899505
AN - SCOPUS:84903629396
SN - 0022-1767
VL - 193
SP - 431
EP - 438
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -