Suppression of experimental colitis in mice by CD11c+ dendritic cells.
BACKGROUND
The innate immune system serves a critical role in homeostasis of the gastrointestinal (GI) tract. Both macrophages (MØs) and dendritic cells (DCs) have been shown to have pathogenic roles in animal models of inflammatory bowel disease. However, studies by several labs have established that resident MØs and DCs within the normal GI tract maintain an immunosuppressive phenotype compared to that seen in other peripheral sites. Recent studies by our lab demonstrated that the depletion of both MØs and DCs before the initiation of dextran sodium sulfate (DSS)-induced colitis resulted in exacerbation of disease, partly caused by increased neutrophil influx.


RESULTS
In this current report, DSS-induced colitis was shown to be significantly more severe when DCs were selectively depleted in mice as indicated by changes in weight loss, stool consistency, rectal bleeding, and histopathology. In contrast to enhanced colitis in MØ/DC-depleted mice, which was associated with increased neutrophil influx, increased colitis in DC-depleted mice was not associated with an increase in neutrophils in the colon, as shown by CXCL1 chemokine levels and myeloperoxidase (MPO) activity. However, increased IL-6 gene and protein expression in colon tissues correlated positively with increased colitis severity in DC-depleted mice compared to colitis in DC-intact mice.


CONCLUSIONS
This study demonstrates that resident DCs can suppress the severity of acute DSS colitis and that regulation of IL-6 production may contribute to DC-mediated control of intestinal inflammation.
Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, College of Medicine, Lexington, Kentucky 40536-0084, USA.
Joseph E
JE
Qualls
Halide
H
Tuna
Alan M
AM
Kaplan
Donald A
DA
Cohen
D000818:Animals; D039521:CD11c Antigen / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control; D003713:Dendritic Cells / Q000276:immunology*; D016264:Dextran Sulfate / Q000008:administration & dosage; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D012720:Severity of Illness Index
D039521:CD11c Antigen; D015850:Interleukin-6; D016264:Dextran Sulfate