Essential role for CD103 in the T cell-mediated regulation of experimental colitis.
The integrin CD103 is highly expressed at mucosal sites, but its role in mucosal immune regulation remains poorly understood. We have analyzed the functional role of CD103 in intestinal immune regulation using the T cell transfer model of colitis. Our results show no mandatory role for CD103 expression on T cells for either the development or CD4+CD25+ regulatory T (T reg) cell-mediated control of colitis. However, wild-type CD4+CD25+ T cells were unable to prevent colitis in immune-deficient recipients lacking CD103, demonstrating a nonredundant functional role for CD103 on host cells in T reg cell-mediated intestinal immune regulation. Non-T cell expression of CD103 is restricted primarily to CD11c(high)MHC class II(high) dendritic cells (DCs). This DC population is present at a high frequency in the gut-associated lymphoid tissue and appears to mediate a distinct functional role. Thus, CD103+ DCs, but not their CD103- counterparts, promoted expression of the gut-homing receptor CCR9 on T cells. Conversely, CD103- DCs promoted the differentiation of IFN-gamma-producing T cells. Collectively, these data suggest that CD103+ and CD103- DCs represent functionally distinct subsets and that CD103 expression on DCs influences the balance between effector and regulatory T cell activity in the intestine.
Annacker
Oliver
O
Sir William Dunn School of Pathology, University of Oxford, OX1 3RE, England, UK.
Coombes
Janine L
JL
Malmstrom
Vivianne
V
Uhlig
Holm H
HH
Bourne
Tim
T
Johansson-Lindbom
Bengt
B
Agace
William W
WW
Parker
Christina M
CM
Powrie
Fiona
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000628:therapy; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018928:Immunity, Mucosal / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D039001:Integrin alpha Chains / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D016207:Cytokines; D039001:Integrin alpha Chains; C091367:alpha E integrins