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Skewed Th1 Responses Caused by Excessive Expression of Txk, a Member of the Tec Family of Tyrosine Kinases, in Patients with Behcet’s Disease

Noboru Suzuki, MD, PhD; Departments of Immunology and Medicine, St. Marianna University, School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
Kazuhiko Nara, MD; Departments of Immunology and Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan
Tomoko Suzuki, MD, PhD; Departments of Immunology and Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa 216-8511, Japan

Reprint Requests: Noboru Suzuki, MD, PhD, Departments of Immunology and Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan, Tel: 81-44-977-8111 (ext 3545), Fax: 81-44-975-3315, E-mail: n3suzuki{at}marianna-u.ac.jp

Behcet’s disease (BD) is characterized by recurrent attacks of uveitis, oral aphtha, genital ulcers and skin lesions. The etiology and pathogenesis of BD are largely unknown. It has been reported that excessive Th1 cell function is involved in the pathogenesis of BD. Previously, we found that Txk, a member of the Tec family of tyrosine kinases, acts as a Th1 cell-specific transcription factor that is involved in the effector function of Th1 cells. Thus, we studied Th1 cytokine production and Txk expression of T-lymphocytes in patients with BD. Peripheral blood lymphocytes produced excessive Th1-associated cytokines including interferon- (IFN-) and interleukin (IL)-12 in patients with BD. Circulating CD3+ and purified CD4+ T cells expressed excessive Txk protein. The extent of IFN- production by the lymphocytes correlated with the expression of Txk protein in the immunoblotting analysis. The majority of cells infiltrating into the skin lesions of patients with BD expressed IFN-. IL-12 and IL-18 were found in the mononuclear cell aggregates in the skin and intestinal lesions of those with BD. Lymphocytes accumulating in the skin and intestinal lesions expressed higher levels of Txk as compared with other Th2-associated diseases. IFN-, IL-18 and IL-12 detected in skin lesions may induce preferential development of Th1 cells in patients with BD. Collectively, Th1 cells expressing Txk and Th1-associated cytokines may play a critical role in the development of skin and intestinal lesions in patients with BD. This review may serve as a reminder of the importance of excessive Th1 cell function in the pathogenesis of BD and may contribute to the discovery of new molecular targets for the development of a specific therapeutic strategy for BD.

Key Words: Behcet’s disease • Th1 cell • Txk • cytokines

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