Suppression of Experimental Colitis in Mice by CD11c+ dendritic cells

JE Qualls, H Tuna, AM Kaplan… - Inflammatory bowel …, 2009 - academic.oup.com
JE Qualls, H Tuna, AM Kaplan, DA Cohen
Inflammatory bowel diseases, 2009academic.oup.com
Background The innate immune system serves a critical role in homeostasis of the
gastrointestinal (GI) tract. Both macrophages (Mϕs) 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 Mϕs 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 Mϕs and DCs …
Background
The innate immune system serves a critical role in homeostasis of the gastrointestinal (GI) tract. Both macrophages (Mϕs) 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 Mϕs 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 Mϕs and DCs before the initiation of dextran sodium sulfate (DSS)-induced colitis resulted in exacerbation of disease, partly caused by increased neutrophil influx.
Methods/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 Mϕ/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.
Oxford University Press