title: Decreased B and T lymphocyte attenuator in Behcet's disease may trigger abnormal Th17 and Th1 immune responses.
abstract: Behcet's disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4(+) T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti-BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses.
authors: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China.
authors: Zi
authors: Z
authors: Ye
authors: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China.
authors: Bolin
authors: B
authors: Deng
authors: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China.
authors: Chaokui
authors: C
authors: Wang
authors: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China.
authors: Dike
authors: D
authors: Zhang
authors: University Eye Clinic Maastricht, Maastricht, the Netherlands.
authors: Aize
authors: A
authors: Kijlstra
authors: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, P. R. China.
authors: Peizeng
authors: P
authors: Yang
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008297:Male; D011971:Receptors, Immunologic / Q000378:metabolism*; D031300:Retinal Vasculitis / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014607:Uveomeningoencephalitic Syndrome / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D011971:Receptors, Immunologic; D000097043:Interleukin-22; C482586:BTLA protein, human