T cell immunoglobulin- and mucin-domain-containing molecule-4 attenuates concanavalin A-induced hepatitis by regulating macrophage.
Tim-4 is expressed primarily on APCs, including macrophages, and has been shown to play a critical role in T cell regulation. However, it remains unclear whether Tim-4 also plays a role in the regulation of macrophage functions. In the present study, we investigated the effects of Tim-4 on macrophage activity in Con A-induced hepatitis in mice. We found that high levels of Tim-4 expression were associated with a diminished serum level of ALT in Con A-induced hepatitis. In addition, adoptive transfer of T4-RAW cells resulted in a significant decrease in ALT levels and Con A-induced liver injuries in mice. Concurrently, T4-RAW cells transfer displayed, markedly decreased apoptosis in liver and depressed TNF-alpha secretion in serum, supporting the hypothesis that Tim-4 protects Con A-induced hepatitis by negatively regulating macrophages. Consistent with the in vivo findings, in vitro studies showed that Tim-4 overexpression in RAW264.7 cells was associated with decreased expression of CD80, CD86, and MHCII molecules and the production of TNF-alpha. Moreover, Tim-4 blockade promoted LPS-induced macrophage activation. In conclusion, these findings indicate that Tim-4 plays an important role in alleviating liver damage by inhibition of macrophage activity. Tim-4 pathway could be a potential target for the treatment of acute hepatitis.
Xu
Liyun
L
Institute of Immunology, Key Laboratory for Experimental Teratology of Ministry of Education, Shandong University School of Medicine, #44 Wenhua Xi Rd., Jinan, Shandong 250012, China.
Qi
Jianni
J
Zhao
Peiqing
P
Liang
Xiaohong
X
Ju
Ying
Y
Liu
Peng
P
Liu
Bing
B
Guo
Chun
C
Zhang
Lining
L
Ma
Chunhong
C
Gao
Lifen
L
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics; D051940:B7-2 Antigen / Q000235:genetics; D002460:Cell Line; D003208:Concanavalin A / Q000633:toxicity; D015536:Down-Regulation / Q000235:genetics; D006505:Hepatitis / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D008262:Macrophage Activation; D008264:Macrophages; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; C500399:TIM-4 protein, mouse; D003208:Concanavalin A; D007371:Interferon-gamma