The role of T cell immunoglobulin mucin domains 1 and 4 in a herpes simplex virus-induced Behçet's disease mouse model.
The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and tolerance. 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 the interaction of TIM-1 and TIM-4 is involved in the regulation of T helper (Th) cell responses and modulation of the Th1/Th2 cytokine balance. Behçet's disease (BD) is a chronic, multisystemic inflammatory disorder with arthritic, intestinal, mucocutaneous, ocular, vascular, and central nervous system involvement. Tim-1 expression was lower in a herpes simplex virus-induced BD mouse model compared to that in asymptomatic BD normal (BDN) mice. Tim-4 expression was higher in BD mice than that in BDN mice. In this study, we investigated the Tim expression in a BD mouse model with BD-like symptoms. Tim-1 and Tim-4 expression was regulated by an expression vector or siRNA injected into the BD mouse model. The Tim-1 vector injected into BD mice resulted in changes in BD-like symptoms and decreased the severity score. Treatment with Tim-4 siRNA also improved BD-like symptoms and decreased the severity score accompanied by upregulation of regulatory T cells. We showed that regulating Tim-1 or Tim-4 affected BD-like symptoms in mice.
Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Suwon 443-721, Republic of Korea.
Ju A
JA
Shim
Department of Dermatology, Ajou University, School of Medicine, Suwon 443-721, Republic of Korea.
Eun-So
ES
Lee
Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Suwon 443-721, Republic of Korea.
Bunsoon
B
Choi
Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Suwon 443-721, Republic of Korea ; Brain Korea 21 Project for Medical Science, Suwon 443-721, Republic of Korea.
Seonghyang
S
Sohn
D000818:Animals; D001528:Behcet Syndrome / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D000072596:Hepatitis A Virus Cellular Receptor 1; D053646:Interleukin-2 Receptor beta Subunit / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D034741:RNA, Small Interfering / Q000235:genetics; D018139:Simplexvirus / Q000472:pathogenicity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D016207:Cytokines; C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; C508022:Il2rb protein, mouse; D053646:Interleukin-2 Receptor beta Subunit; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C500399:TIM-4 protein, mouse