Alopecia areata is a chronic autoimmune hair loss disorder that affects 0.2-2 % of population. Although alopecia areata is a non-fatal disease, the disease itself and the treatment complication can cause significant morbidity. Clinical and laboratory data from studying of human patients suggests that alopecia areata may be caused by autoreactive lymphocytes, particularly CD8+ T lymphocytes. Although passive transfer experiments delineated the hair loss process once the autoreactive T lymphocytes are formed, the step-by-step immunological sequence of events accounting for the initiation, progression, and maintenance of the disease remain unclear. Moreover, the antigen targeted by the autoreactive lymphocytes remains unknown. Furthermore, currently there is no active experimental animal model of alopecia areata for dissecting these step by-step events. The PI, Lawrence S. Chan, M.D., was trained as a fellow in Immuno-dermatology under Dr. Kevin D. Cooper, a cellular immunologist at the Univ. of Michigan. For the current proposal, the PI aims at characterizing a newly generated mouse model of hair loss disorder, induced by subcutaneous immunization of a mouse hair follicle basement membrane component. This newly generated active mouse model of hair loss disorder has clinical and histologic findings resembling the human disease alopecia areata. Some affected mice developed autoantibodies to the immunogens. The same strain of mice developed autoreactive T cell response to the self proteins. The PI proposes to authenticate this model as a mouse model for human alopecia. areata with the following specific aims: 1). Authentication of the autoimmune nature of this hair loss disorder model 2). Characterization of the effector immune cell types. If established as a model of human disease, it may shed light to the pathogenesis of alopecia areata in human patients and thereby lead to eventual target-specific immunological treatments for human patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Exploratory/Developmental Grants (R21)
Project #
7R21AR048438-02
Application #
6599254
Study Section
Special Emphasis Panel (ZAR1-RJB-B (O1))
Program Officer
Moshell, Alan N
Project Start
2001-09-28
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$77,935
Indirect Cost
Name
University of Illinois at Chicago
Department
Dermatology
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Chen, Lin; Lin, Shao-xia; Amin, Sanober et al. (2010) VCAM-1 blockade delays disease onset, reduces disease severity and inflammatory cells in an atopic dermatitis model. Immunol Cell Biol 88:334-42
Chen, L; Overbergh, L; Mathieu, C et al. (2008) The development of atopic dermatitis is independent of Immunoglobulin E up-regulation in the K14-IL-4 SKH1 transgenic mouse model. Clin Exp Allergy 38:1367-80
Chen, Lin; Marble, Deborah J; Agha, Rania et al. (2008) The progression of inflammation parallels the dermal angiogenesis in a keratin 14 IL-4-transgenic model of atopic dermatitis. Microcirculation 15:49-64
Chen, Lin; Lin, Shao-xia; Agha-Majzoub, Rania et al. (2006) CCL27 is a critical factor for the development of atopic dermatitis in the keratin-14 IL-4 transgenic mouse model. Int Immunol 18:1233-42
Chen, L; Lin, S-X; Overbergh, L et al. (2005) The disease progression in the keratin 14 IL-4-transgenic mouse model of atopic dermatitis parallels the up-regulation of B cell activation molecules, proliferation and surface and serum IgE. Clin Exp Immunol 142:21-30
Chen, Lin; Martinez, O; Venkataramani, P et al. (2005) Correlation of disease evolution with progressive inflammatory cell activation and migration in the IL-4 transgenic mouse model of atopic dermatitis. Clin Exp Immunol 139:189-201
Xu, Luting; Olivry, Thierry; Chan, Lawrence S (2004) Molecular cloning of a cDNA encoding the porcine type XVII collagen noncollagenous 16 A domain and localization of the domain to the upper part of porcine skin basement membrane zone. Vet Dermatol 15:146-51
Chen, L; Martinez, O; Overbergh, L et al. (2004) Early up-regulation of Th2 cytokines and late surge of Th1 cytokines in an atopic dermatitis model. Clin Exp Immunol 138:375-87
Berlin, Alexander L; Paller, Amy S; Chan, Lawrence S (2002) Incontinentia pigmenti: a review and update on the molecular basis of pathophysiology. J Am Acad Dermatol 47:169-87; quiz 188-90