Thursday, April 25, 2024
4/25/2024
Project Summary Tissue destruction and bone loss occur due to uncontrolled and progressing inflammation within gingival tissue. Resolution of inflammation is necessary to return to a homeostatic state and to initiate reparative/regenerative functions within mucosal tissues. We examined chronically inflamed gingival tissues to determine if T cells with anti-inflammatory function (regulatory T cells; Treg) and tissue-repair function (IL-17 and IL-22 secreting T cells; Th17/22) are lost or preserved during inflammation. We found that Treg and Th17/22 CD4 T cell populations were still intact in the inflamed gingiva suggesting that there is a retained intrinsic ability to resolve inflammation. We now propose to interrogate different mechanisms that could interfere with Th17/22 and Treg promoted resolution of inflammation. Of note, some IL-17 is critical to maintain barrier immunity, while excess IL-17 drives tissue pathology, thus the presence Th17 cells must be interpreted carefully and in context of the T cell population. We consider and propose to test several different possibilities: tissue damaging effector T cells may counteract ongoing repair efforts, Treg and Th17/22 functions may not be properly elicited in the inflamed gingiva and repair efforts may be actively suppressed by APCs. The goal of our proposed experiments is to gain a better understanding of the immunological mechanisms that perpetuate a state of inflammation and prevent resolution of inflammation in chronically inflamed gingiva. Identifying these immunological mechanisms is relevant as it will help provide insight to ultimately allow for selective therapeutic targeting of immune cell subsets to treat chronically inflamed oral tissues.
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