title: The expression and anatomical distribution of BTLA and its ligand HVEM in rheumatoid synovium.
abstract: Co-inhibitory signaling from B and T lymphocyte attenuator (BTLA) can suppress lymphocyte activation and maintain peripheral tolerance. However, the expression and anatomical distribution of BTLA and its ligand, herpesvirus entry mediator (HVEM), in rheumatoid arthritis (RA) synovium have not been reported. In this study, we analyzed the expression of HVEM and BTLA in RA synovium by immunohistochemistry, and our results showed that both factors were observed in all four cases of RA samples. At the cellular level, both HVEM and BTLA were found on the cell membrane and in the cytoplasm. Fluorescence dual staining demonstrated that HVEM was chiefly on CD3(+) T cells, CD68(+) macrophages, and to a lesser extent was found on CD31(+) endothelial cells. Similarly, the expression of BTLA was observed on infiltrated CD3(+) T cells and CD68(+) macrophages. The co-expression of HVEM and BTLA with some members of the B7 family in these sections was also analyzed, and the results showed that HVEM antigen was also found on B7-H3(+) capillaries, while it was absent on B7-H1(+), B7-DC(+), B7-H4(+), and Z39Ig(+) cells. Interestingly, BTLA was observed on B7-H1(+), B7-H4(+), and HVEM(+) cells in the synovium. The characteristic expression and distribution of BTLA/HVEM in the synovium indicated that their signaling probably affects the pathogenesis of RA, and a clear understanding of their functional roles may further elucidate the pathogenesis of this disease.
authors.affiliation: Department of Orthopedics, Affiliated Hospital of Chifeng University, Inner Mongolia 024000, People's Republic of China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Shang
authors.forename: Guoning
authors.initials: G
authors.lastname: Guo
authors.forename: Qifu
authors.initials: Q
authors.lastname: Cui
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ruan
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Chen
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D060887:B7 Antigens / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000378:metabolism*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000378:metabolism*; D015398:Signal Transduction; D013583:Synovial Membrane / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D060887:B7 Antigens; D017252:CD3 Complex; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; C482586:BTLA protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C506028:TNFRSF14 protein, human