The role of T cell Immunoglobulin Mucin domain in Herpes Simplex Virus-induced Behçet’s Disease mouse model
The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and tolerance. Individual TIM family members may serve as susceptibility markers for asthma, allergies and autoimmune diseases, as well as potential cell surface markers for T helper type (Th)1 and Th2 T cells. TIM-1 plays an important role in the regulation of immune responses and the development of autoimmune diseases. TIM-4 is a natural ligand of TIM-1, and interaction of TIM-1 and TIM-4 is involved in the regulation of Th cell responses and the modulation of the Th1/Th2 cytokines balance. TIM-4 expression was increased in patients with systemic lupus erythematosus (SLE). It has been also reported that TIM-3 expression was higher in patients with rheumatoid arthritis compared to controls. Further, Galectin-9 (Gal-9) has been identified as a TIM-3 ligand (L) and the TIM-3-TIM-3L interaction serves as a specific down-regulator of the Th1 immune response. Behçet’s disease (BD) is a chronic, multisystemic inflammatory disorder with arthritic, gastrointestinal, mucocutaneous, ocular, vascular, and central nervous system involvement. In herpes simplex virus induced BD mouse model, the expression of Tim-1 and Gal-9 was lower levels compared to asymptomatic BD normal (BDN) mice. The expression of Tim-3 and Tim-4 was higher in BD mice than BDN mice. In addition, Tim-1 vector injected BD mice showed changes of BD-like symptoms and decreased the severity score. Again, treatment with Tim-4 siRNA also improved the BD-like symptoms and decreased the severity score accompanied with up-regulation of regulatory T cells (Treg). Furthermore, administration of Gal-9 improved the BD-like symptoms, decreased the severity score, and increased Treg cells. In addition, Gal-9 induced improvement was associated with down-regulation of pro-inflammatory cytokines and induction of apoptosis. In the present study, we showed that the regulation of Tim-1 or Tim-4 affected the BD-like symptoms and Tim-3-Tim-3L interaction improved the inflammatory symptoms in BD mice.
Tim-1, Tim-3, Tim-4, Galectin-9, Herpes simplex virus-induced systemic inflammation, Behçet’s Disease mouse model, 베체트병 마우스 모델, 단순포진바이러스
Networked Digital Library of Theses and Dissertations