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1566958 
Journal Article 
The Expression and Anatomical Distribution of BTLA and Its Ligand HVEM in Rheumatoid Synovium 
Shang, Y; Guo, G; Cui, Q; Li, J; Ruan, Z; Chen, Y 
2012 
Yes 
Inflammation
ISSN: 0360-3997
EISSN: 1573-2576 
35 
3 
1102-1112 
22179929 
WOS:000303382400040 
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. 
pyranocoumarin; lipopolysaccharide; nuclear factor-kappa B; signal transducer and activator of transcription 3; nitric oxide; tumor necrosis factor-alpha; interleukin-6; macrophage