Crohn's disease (CD) is a chronic inflammatory disease of the intestinal tissue that affects over 3 million people in the US. Periodontal disease (PD) is a chronic inflammation of the gingival epithelium, ultimately leading to the destruction of the supporting tissues of the teeth and loss of alveolar bone, that affects over 45% of older adults in the US. Patients with CD have a significantly higher incidence of PD than the general population (up to 90%), and the severity and extent of PD is greater in CD patients than in intestinally healthy individuals. While there are similarities between the two diseases with respect to mediators of immunity and bacterial growth and colonization, the link between the two is unknown. Elucidation of this relationship can lead to a more effective personalized medicine approach to treat these two diseases. It is clear that innate immunity plays an important role in the pathogenesis of both CD and PD. A major regulator of innate immunity is the innate lymphoid cell (ILC). There are three types of ILC (ILC1, ILC2 and ILC3), based on the cytokines they express. Mucosal tissues are generally populated by ILC2 and ILC3, with ILC1 being present at low frequency. In CD lesions, however, there is a phenotype switch leading to a shift from ILC3 to ILC1. While only recently discovered in periodontal tissues, a similar identification of ILC1 was observed in the gingiva. Therefore, it is hypothesized that patients with both CD and PD suffer from the same immune dysfunction, which is related to the regulation of ILC phenotype. The purpose of this exploratory proposal is to obtain sufficient data to support an in-depth study to address this hypothesis, and ultimately identify the mechanism that underlies the pathogenesis of these two disorders. To this end, two aims are proposed: 1) Define the ILC phenotype in diseased and healthy sites in patients with CD and PD; and 2) Characterize the change in ILC phenotype in mouse models of CD and PD. Successful completion of these aims will demonstrate a role for ILC plasticity in the interrelationship between CD and PD. This will then provide a strong foundation upon which to develop an in-depth study to define the mechanism which underlies the susceptibility to both CD and PD.

Public Health Relevance

Patients with Crohn's disease have a much higher incidence of periodontal disease than the general population, suggesting a link between the two diseases. We propose to examine a potential reason for this link, which involves the changes in cells of the immune system that are found in both intestinal tissue and in the gums. Successful demonstration of this relationship can lead to a more effective personalized medicine approach to treating both of these diseases.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Exploratory/Developmental Grants (R21)
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Oral, Dental and Craniofacial Sciences Study Section (ODCS)
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Chander, Preethi
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University of Mississippi Medical Center
United States
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