Loss of CD103+ intestinal dendritic cells during colonic inflammation.
OBJECTIVE
To investigate possible differences in dendritic cells (DC) within intestinal tissue of mice before and after induction of colitis.


METHODS
Mucosal DC derived from intestinal tissue, as well as from mesenteric lymph nodes and spleen, were analyzed by fluorescence activated cell sorting (FACS) analysis. Supernatants of these cells were analyzed for secretion of different pro- and anti-inflammatory cytokines. Immunohistochemistry and immunofluorescence were performed on cryosections of mucosal tissue derived from animals with colitis as well as from healthy mice.


RESULTS
It was shown that DC derived from healthy intestinal lamina propria (LP) represented an immature phenotype as characterized by low-level expression of costimulatory cytokines. In contrast to DC from spleen and mesenteric lymph nodes (MLN) that secreted proinflammatory cytokines, LP-DC produced high levels of the anti-inflammatory cytokine IL-10. After induction of murine colitis in a CD4(+)CD62L(+) transfer model or in chronic dextran sulfate sodium-colitis, a marked increase of activated CD80(+) DC could be observed within the inflamed colonic tissue. Interestingly, in contrast to splenic DC, a significant population of DC within MLN and colonic LP expressed the mucosal integrin CD103 which was lost during colitis.


CONCLUSIONS
The constitutive secretion of anti-inflammatory cytokines by immature DC within the intestinal LP might regulate the homeostatic balance between mucosal immunity and tolerance. CD103(+) DC could mediate this important function.
Strauch
Ulrike G
UG
Department of Internal Medicine I, University of Regensburg, D-93053 Regensburg, Germany. ulrike.strauch@klinik.uni-regensburg.de
Grunwald
Nicole
N
Obermeier
Florian
F
Gürster
Sonja
S
Rath
Heiko C
HC
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015536:Down-Regulation; D005434:Flow Cytometry; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007150:Immunohistochemistry; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008856:Microscopy, Fluorescence; D010641:Phenotype; D013154:Spleen / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D039521:CD11c Antigen; D018836:Inflammation Mediators; D039001:Integrin alpha Chains; C091367:alpha E integrins; D019041:L-Selectin; D016753:Interleukin-10; D007371:Interferon-gamma; D016264:Dextran Sulfate