The skin is the primary barrier protecting other organs and internal tissues from the external environment. Epicutaneous application of some environmental chemicals results in a T cell- mediated inflammatory response termed allergic contact dermatitis or contact hypersensitivity (CHS). Most studies examining the immmunpathogenesis of allergic contact dermatitis have focused on the induction phase of the response. Much less is known about the cellular and molecular requirements for elicitation of allergic contact dermatitis once sensitization has occurred. In this proposal, we hypothesize that: the requirement of antigen presenting cells and the costimulatory molecules that they express for induction and elicitation of CHS reactions are different. We will examine this issue in mice by assessing the types of cells that can serve as antigen presenting cells for elicitation of the response. MHC class I and class II antigens that are known to be important for induction of allergic contact dermatitis will be examined for their role during the elicitation phase of the response. Based on our preliminary data indicating that transfer of hapten primed T cells to ICAM-1 deficient mice elicited a reduced CHS response and the development of hapten primed T cells in the mice was impaired, the role of ICAM-1 in the elicitation of CHS will be determined. We will also evaluate whether those antigen-presenting cells that are unable to elicit CHS have the capacity to desensitize animals that have already been sensitized to hapten. Because our current results indicate that CHS is significantly increased in gammadeltaT cell deficient mice, the potential regulatory effects of gammadeltaT cells will also be evaluated. On a basic level, the results will provide new information concerning the pathogenesis of allergic contact dermatitis and interactions between the skin and the immune system. On a clinical level, the information should be useful for the development of new specific strategies for the prevention and treatment of this common skin disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR046256-02
Application #
6171484
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Moshell, Alan N
Project Start
1999-08-01
Project End
2003-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
2
Fiscal Year
2000
Total Cost
$167,991
Indirect Cost
Name
University of Alabama Birmingham
Department
Dermatology
Type
Schools of Medicine
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
He, Donggou; Li, Hui; Yusuf, Nabiha et al. (2012) IL-17 mediated inflammation promotes tumor growth and progression in the skin. PLoS One 7:e32126
He, Donggou; Li, Hui; Yusuf, Nabiha et al. (2010) IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells. J Immunol 184:2281-8
He, Donggou; Wu, Lizhi; Kim, Hee Kyung et al. (2009) IL-17 and IFN-gamma mediate the elicitation of contact hypersensitivity responses by different mechanisms and both are required for optimal responses. J Immunol 183:1463-70
Kim, Hee Kyung; Zhang, Hong; Li, Hui et al. (2008) Slit2 inhibits growth and metastasis of fibrosarcoma and squamous cell carcinoma. Neoplasia 10:1411-20
Yusuf, Nabiha; Timares, Laura; Seibert, Megan D et al. (2007) Acquired and innate immunity to polyaromatic hydrocarbons. Toxicol Appl Pharmacol 224:308-12
He, Donggou; Wu, Lizhi; Kim, Hee Kyung et al. (2006) CD8+ IL-17-producing T cells are important in effector functions for the elicitation of contact hypersensitivity responses. J Immunol 177:6852-8
Guan, Hongbing; Zu, Guorui; Xie, Yi et al. (2003) Neuronal repellent Slit2 inhibits dendritic cell migration and the development of immune responses. J Immunol 171:6519-26
Guan, Hongbing; Zu, Guorui; Slater, Marlon et al. (2002) GammadeltaT cells regulate the development of hapten-specific CD8+ effector T cells in contact hypersensitivity responses. J Invest Dermatol 119:137-42
Xu, H; Guan, H; Zu, G et al. (2001) The role of ICAM-1 molecule in the migration of Langerhans cells in the skin and regional lymph node. Eur J Immunol 31:3085-93
Xu, H; Bjarnason, B; Elmets, C A (2000) Sensitization versus elicitation in allergic contact dermatitis: potential differences at cellular and molecular levels. Am J Contact Dermat 11:228-34

Showing the most recent 10 out of 11 publications