Ultraviolet B radiation is a potent immunosuppressive agent that inhibits cell-mediated immune responses.This biologic property contributes in a major way to the growth and development of UV-induced skin cancers.Toll-like receptors, one component of innate immune system are intricately associated with a number ofdermatologic conditions. Recent experiments from my laboratory suggest that innate immunity, especiallytoll like receptor 4 (TLR4), may play an important role in photoimmunological processes. The hypothesisthat I will test in this proposal is that UV-induced regulatory T-cells (Treg) act to inhibit the developmentand/or function of IFN-D producing T-cells (TC1) but not IL-17 producing T-cells (TC17). Since TLR4deficiency directs the cell-mediated immune response towards IL-17 producing T-cells, the inability of UVinducedTreg cells to inhibit Tc17 cells results in fewer UV-induced tumors in TLR4 deficient mice. Toaddress these issues, three specific aims are proposed. First, experiments will be conducted to assesswhether regulatory T-cells develop in TLR4 knockout mice after UVB radiation exposure, and, if so, theirphenotype and cytokine profile will be characterized. Then, studies will be performed to determine whyregulatory T-cells either do not develop or are non-functional in TLR4 deficient mice. Finally, the implicationsof resistance of TLR4 deficient mice to UVB-induced immunosuppression for photocarcinogenesis will beassessed. The ultimate goal of these studies is to identify genetic loci that are involved in UV-inducedimmune suppression and to exploit that knowledge to develop immunopreventive and immunotherapeuticapproaches for photoimmunosuppression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Center Core Grants (P30)
Project #
5P30AR050948-05
Application #
7691492
Study Section
Special Emphasis Panel (ZAR1-AAA-G (J1))
Project Start
2008-08-01
Project End
2009-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
5
Fiscal Year
2008
Total Cost
$45,218
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Frugé, Andrew D; Van der Pol, William; Rogers, Laura Q et al. (2018) Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial. J Acad Nutr Diet :
Frugé, Andrew D; Cases, Mallory G; Howell, Carrie R et al. (2018) Fingernail and toenail clippings as a non-invasive measure of chronic cortisol levels in adult cancer survivors. Cancer Causes Control 29:185-191
Stoll, Matthew L; Pierce, M Kathy; Watkins, Jordan A et al. (2018) Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of arthritis. Genes Immun :
Frugé, Andrew D; Ptacek, Travis; Tsuruta, Yuko et al. (2018) Dietary Changes Impact the Gut Microbe Composition in Overweight and Obese Men with Prostate Cancer Undergoing Radical Prostatectomy. J Acad Nutr Diet 118:714-723.e1
Koo, Hyunmin; Hakim, Joseph A; Powell, Mickie L et al. (2017) Metagenomics approach to the study of the gut microbiome structure and function in zebrafish Danio rerio fed with gluten formulated diet. J Microbiol Methods 135:69-76
Garcia, S S; Blackledge, M S; Michalek, S et al. (2017) Targeting of Streptococcus mutans Biofilms by a Novel Small Molecule Prevents Dental Caries and Preserves the Oral Microbiome. J Dent Res 96:807-814
Larson, Thomas R; Yother, Janet (2017) Streptococcus pneumoniae capsular polysaccharide is linked to peptidoglycan via a direct glycosidic bond to ?-D-N-acetylglucosamine. Proc Natl Acad Sci U S A 114:5695-5700
Brawner, K M; Kumar, R; Serrano, C A et al. (2017) Helicobacter pylori infection is associated with an altered gastric microbiota in children. Mucosal Immunol 10:1169-1177
Kim, T; Holleman, C L; Ptacek, T et al. (2017) Duodenal endoluminal barrier sleeve alters gut microbiota of ZDF rats. Int J Obes (Lond) 41:381-389
Sharma, Nirmal S; Wille, Keith M; Athira, S et al. (2017) Distal airway microbiome is associated with immunoregulatory myeloid cell responses in lung transplant recipients. J Heart Lung Transplant :

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