Abstract
In summary, CD1d is expressed in a polarized manner in biochemically distinct forms on human and rodent IECs. Functional studies in rodents would suggest that activation of CD1d-NK-T-related pathways leads to the generation of immunoregulatory factors that are both anti-inflammatory and barrier-enhancing; characteristics that would be quite beneficial to the perturbations associated with IBD. Our studies would suggest that activation of CD1d on IECs in either an NK-Tdependent or -independent fashion leads to the production of cytokines such as IL-10, which can directly regulate IEC barrier function in an autocrine manner. It is therefore possible that glycolipid antigens, perhaps derived from luminal microbial antigens, may either directly stimulate CDld on IECs or indirectly stimulate IECs through presentation of these glycolipid antigens to local CDld-restricted T cells such as the NK-T cell. These studies further suggest that NK-T cells may be a novel type of immunoregulatory cell relevant to IBD pathogenesis. 23 How these insights relate to immunotherapeutic approaches in IBD remains to be established. However, it is becoming increasingly clear that rationalizing IBD therapy around the sequence of immunologic events associated with IBD pathogenesis is extremely important (Table 1).
