Increased expression of T cell immunoglobulin and mucin domain 3 aggravates brain inflammation via regulation of the function of microglia/macrophages after intracerebral hemorrhage in mice

Background: microglia/macrophages are known to play important roles in initiating brain inflammation after spontaneous intracerebral hemorrhage (ich). t cell immunoglobulin and mucin domain-3 (tim-3) have been proven to play a critical part in several inflammatory diseases through regulation of both adaptive and innate immune responses. tim-3 can be expressed by microglia/macrophages and regulates their function in the innate immune response. however,the effect of tim-3 on inflammatory responses following ich is unclear.methods: in this study,we investigated tim-3 expression,the inflammatory cytokines tumor necrosis factor-α (tnf-α) and interleukin-1β (il-1β),and brain water content in peri-hematomal brain tissue at 12 hours and at 1,3,5,and 7 days post-ich in wild type (wt) ich and tim-3-/- ich mice. the numbers of tim-3 positive cells,astrocytes,neutrophils and microglia/macrophages were detected using immunofluorescence staining. cytokines were measured by elisa. double immunoflurorescence labeling was performed to identify the cellular source of tim-3 expression. mouse neurological deficit scores were assessed through animal behavior.results: expression of tim-3 increased early in mouse peri-hematomal brain tissue after autologous blood injection,peaked at day 1,and was positively correlated with the concentrations of tnf-α,il-1β,and brain water content. tim-3 was predominantly expressed in microglia/macrophages. compared with wt mice,tim-3-/- mice had reduced ich-induced brain inflammation with decreased tnf-α and il-1β,cerebral edema and neurological deficit scores. moreover,tim-/- inhibited activation of microglia/macrophages. the number of activated microglia/macrophages in tim-3-/- ich mice was much lower than that in wt ich mice.conclusions: our findings demonstrate that tim-3 plays an important role in brain inflammation after ich,and may be a potential treatment target. © 2013 xu et al.; licensee biomed central ltd.