engleski

Interleukin-33 enhances CD8+ T cell response in MCMV infection

Interleukin-33 (IL-33) is a recently identified member of IL-1 cytokine family (Schmitz et al., 2005). It is expressed in the nucleus of nonhematopoietic cells, such as fibroblasts, epithelial and endothelial cells of various tissues, following pro-inflammatory stimulation and is thought to be released on cell necrosis as an alarmin. The IL-33 receptor consists of ST2 and IL-1 receptor accesory protein. By differential splicing, the ST2 gene encodes at least 3 isoforms of protein, a soluble form, a variant and a membrane-bound ST2 which is a member of Toll-like receptor (TLR) family. Although the receptor is expressed by many cell types, membrane-bound ST2 expression is highest on mast cells and activated T helper 2 (TH2) cells. Many evidences support an important role of IL-33 in TH2 cell-mediated immune responses. Interestingly, ST2 is also found on NK and NKT cells, which respond to IL-33 with increased IFN-γ production, suggesting a role for IL-33/ST2 in innate TH1 type immune responses (Smithgall et al., 2008). Recently was shown that IL-33 is necessary for CD8+ T cell (CTL) responses to lymphocytic choriomeningitis virus (Bonilla et al., 2012). We studied role of IL-33/ST2 signaling in murine cytomegalovirus (MCMV) model. ST2-deficient (ST2-/-) mice showed weaker CTL response to MCMV infection. Mice had lower percentages of virus-specific CD8+ T cells, decreased IFN-γ production and decreased activation marker expression. These results indicate that IL-33 signals through ST2 receptor to amplify effector T cell response to MCMV. Many questions still remain to be answered regarding IL-33 role in viral infections. However, the ability to target numerous immune cell types and to induce cytokine and chemokine production underlines its potential in influencing the outcome of a wide range od diseases.

IL-33; ST2; MCMV; CD8 T cell

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