Role of indoleamine 2,3‐dioxygenase in an inflammatory model of murine gingiva

Background and Objective Indoleamine 2,3‐dioxygenase (IDO) is one of the major pathways for metabolism of tryptophan in a variety of cells, including immune cells. Increasing evidence indicates that IDO is a critical player in establishing the balance between immunity and tolerance and ultimately in the maintenance of homeostasis. By inducing inflammation in gingival tissue, we tested the hypothesis that IDO is a pivotal player in regulating the immune and inflammatory responses of gingiva. Material and Methods We utilized the IDO knockout mouse model in conjunction with lipopolysaccharide (LPS)‐induced inflammation. Accordingly, wild‐type and IDO knockout mice were injected with LPS or vehicle in the anterior mandibular gingiva, twice over a 2‐wk period, which was followed by procurement of gingival tissue for histopathology and preparation of tissue for flow cytometry‐based studies. Results Clinical and histological examinations revealed a marked adverse impact of IDO deficiency on gingival inflammation. These observations were consistent with a more marked increase in the number of cells positive for the proinflammatory cytokine interleukin (IL)‐17, but no significant change in the number of cells positive for the anti‐inflammatory cytokine IL‐10, in LPS‐treated IDO knockout mice. Consistent with the more marked proinflammatory impact of IDO deficiency, the percentage of regulatory T cells was much reduced in gingival tissue of LPS‐treated IDO knockout mice than in gingival tissue of wild‐type mice. These proinflammatory changes were accompanied with a prominent increase in apoptotic and necrotic cell death in gingival tissue of IDO knockout mice compared with wild‐type mice. Conclusion Collectively, our findings support a major role for IDO in the development of gingival inflammation, as an example of an inflammatory condition, and lay the foundation for subsequent studies to explore it as a novel immunotherapy target.