The Role of Dendritic Cells in the Pathogenesis of Ulcerative Colitis
Berndt, Bradford E.
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Ulcerative colitis (UC) involves a malfunctioning immune response to commensal bacteria within the gastrointestinal tract. Normally, these bacteria are treated as non-pathogenic; however, UC patients are plagued with an active inflammatory immune response that treats them like harmful pathogens. Recent studies have shown that dendritic cells (DC) play a role in the pathogenesis of UC, but their direct involvement in disease progression is unknown. The aim of this study was to assess the role of mature and immature DC in UC. Mature and immature DC were isolated from C57BL/6 mice and separated based upon their adherence to tissue culture plates. Surface marker expressions were measured by FACS analysis, confirming the identity of adherent and non-adherent DC as immature and mature, respectively. The abilities of DC to proliferate T -cells was also assessed, showing that immature DC lower the proliferation rate of mature DC, inferring they would lower disease severity. The role of DC in UC was assessed in vivo using a dextran sodium sulfate salt-induced colitis murine model. Mice treated with mature DC experienced higher disease severity than mice treated with immature DC and a control group, which experienced similar disease responses. Furthermore, a transgenic CDllc-DTR/GFP DC knockout mouse model showed that selective ablation of DC lead to nearly complete resistance of DSS-colitis development. The results of this study confirm that DC are involved in UC pathogenesis and suggest that mature DC are responsible for the development of UC, and hence are a promising future therapeutic target.With honors.