Differential Expression of T Cell Immunoglobulin- and Mucin-Domain-Containing Molecule-3 (TIM-3) According to Activity of Behçet's Disease

BACKGROUND: T cell immunoglobulin mucin-3 (TIM-3) is recently described as a TH1-associated cell surface molecule that regulates TH1 responses and promotes tolerance in mice. Increased TH1 immune response has been known as one possible pathogenesis of a chronic inflammatory multisystemic disorder, Behçet’s disease (BD). However, TIM-3 expression and function in BD has not been investigated. PURPOSE: In this study, its was examined that the surface expression of TIM-3, the expression of TIM-3 protein and the TIM-3 mRNA in peripheral blood mononuclear cells from Behçet’s disease patients, and evaluated the TIM-3 expression pattern according to clinical disease activity. METHODS: Behçet’s patients (n=67), healthy control (n=13) and psoriasis patients (n=14) were involved. Immunologic profile of Korean patients, especially in relation to T cell immunity was examined by flow cytometry. The expression of TIM-3 as well as CD4, CD8, CD11b and CD56 in peripheral blood mononuclear cells (PBMC) was assessed by flow cytometry. BD group was divided according to the disease activity. TIM-3 expression was also compared between BD in active state and BD in remission state. Western blot analysis was performed to evaluated TIM-3 protein. TIM-3 expression after simulation of PBMCs was analyzed by flow cytometry. At the transcript level, the expression of TIM-3 was assessed by quantitative RT-PCR. The immunohistochemical analysis was done in cutaneous lesion with anti-TIM-3 antibody and anti-CD4 antibody. RESULTS: Disease activity markers, ESR and CRP, were elevated in the blood samples from active BD compared to inactive BD. The surface expression of TIM-3 molecule was significantly upregulated in Behçet’s disease patients compared with healthy controls by flow cytometry and the stable BD had a tendency to show higher TIM-3 than the active BD. The immunohistochemical study in cutaneous lesion of BD showed the co-localization of TIM-3+ cells and CD4+ cells in inflammatory site. Western blot analysis also showed the upregulated expression of TIM-3 protein in BD compared to control. Even in each patient, according to his disease activity, the expression of TIM-3 was changed, showing a higher TIM-3 expression in remission state than in active state. In leukocytes subpopulation, there were no significant differences in CD4, CD11b, and CD56 cells except CD8 cells decreased in BD and psoriasis. The mean expression of TIM-3 molecule in CD8+ and CD56+ cells was significantly increased in BD compared with controls. However the correlation between TIM-3 frequency and TIM-3 expression in CD4 cells was highest among leukocyte subpopulations. The stimulation of PBMC with anti-CD3, CD28 antibody in presence of IL-2, could not up-regulate the TIM-3 expression in BD patients with simulation time and TIM-3 expression in CD4+ and CD8+ cells were not changed after stimulation, too. The transcription level analysis of PBMCs from BD patients revealed significantly higher mRNA expression of TIM-3 compared with controls. Moreover, in the same patient, TIM-3 mRNA expression was significantly altered according to disease activity, increasing TIM-3 mRNA in active state compared with remission state. CONCLUSION: This study may imply the differential expression of human TIM-3 molecules by the PBMCs of TH1-driven Behçet’s disease according to disease activity and suggest that there were altered kinetics in the expression of TIM-3 molecule and TIM-3 mRNA in PBMCs that might modulate immunologic response in Behçet’s disease.

Author dc:creator

• 이, 중선

Contributors dc:contributor

• 이, 은소
• 대학원 의학과
• 104547

• Behçet’s disease
• Disease activity
• T cell immunoglobulin and mucin (TIM)-3

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000009766
000000009766

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/1323