Pregnant women are more prone to develop exacerbated gingival inflammation, which is known as pregnancy gingivitis. Inflammation and oral pathogenic bacteria infiltration during pregnancy are detrimental to pregnant women's health and negatively impact on their life quality, and can cause adverse pregnancy outcomes in some cases. Using a modified ligation induced periodontal disease model, our preliminary data implies that the gingival inflammation during pregnancy is linked with lower number of Tregs, one subset of T cells critical for host immune regulation. This proposal hypothesizes that host Tregs proliferate in response to pathogen infection to prevent excessive immune responses, but the process is down-regulated during pregnancy. This down-regulation of Treg development is responsible for the disrupted immune homeostasis and gingival inflammation. This notion will be tested using in vitro analysis and in vivo mouse model.
In Aim 1, we will determine the effect of pregnancy on pathogen-induced Treg number and function. Pregnant mice will be ligated and infected with pathogens to determine the number as well as the immune suppressive function of induced Tregs; detailed mechanisms of the regulation on Treg proliferation will also be determined.
Aim 2 is expected to investigate the role of Tregs in the gingival inflammation during pregnancy. Depletion of Tregs, as well as adoptive transfer of Tregs into pregnant mice, will reveal the effect of Tregs on the gingival inflammation. The objective is to reveal the regulation of infection-induced Treg development by pregnancy status, and the effect of this regulation on gingival inflammation during pregnancy. The goal of the project is to not only pinpoint the critical cell type in the disease, but also provide information for the pathogenesis and future cure of the disease, therefore significantly improving woman health. Moreover, another goal of current proposal is to enhance the research and training environment for the students in our school by exposing more students to the concept and technologies for oral biology research and foster next generation of scientists.

Public Health Relevance

Pregnant women are prone to more prevalent and more severe gingival inflammation. This application proposes to investigate the regulation of infection-driven Treg development during pregnancy and its role in gingival inflammation. This work is expected to pinpoint the role of dysregulation of Treg development in the gingival inflammation during pregnancy.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Academic Research Enhancement Awards (AREA) (R15)
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Special Emphasis Panel (ZRG1-MOSS-U (82))
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Melillo, Amanda A
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University of Louisville
Schools of Dentistry
United States
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Zhou, Wei; Su, Li; Duan, Xingyu et al. (2018) MicroRNA-21 down-regulates inflammation and inhibits periodontitis. Mol Immunol 101:608-614
Duan, Xingyu; Hays, Aislinn; Zhou, Wei et al. (2018) Porphyromonas gingivalis induces exacerbated periodontal disease during pregnancy. Microb Pathog 124:145-151
Yin, Hui; Zhou, Huaxin; Kang, Yi et al. (2016) Syk negatively regulates TLR4-mediated IFN? and IL-10 production and promotes inflammatory responses in dendritic cells. Biochim Biophys Acta 1860:588-98