engleski

Deletion of IL-33 receptor reduces NK cell and CD8 T cell responses to herpesvirus infection

Interleukin-33 (IL-33), a recently identified member of IL-1 cytokine family, serves as a ligand for the ST2 receptor (Schmitz et al, Immunity, 2005). Following pro-inflammatory stimulation, it is expressed in nonhematopoietic cells and released on cell necrosis as an alarmin. Although ST2 receptor is expressed by many cell types, its expression is highest on mast cells and activated T helper 2 (TH2) cells where it participates in TH2 immune responses by stimulating production of IL-5, IL-6, IL-13 and GM-CSF. NK and NKT cells also respond to IL-33 with increased IFN-γ production, suggesting its role in TH1 immune response, as well (Smithgall et al, Int Immunol, 2008). Recently it was shown that IL-33 is necessary for CD8 T cell (CTL) responses to lymphocytic choriomeningitis virus (Bonilla et al, Science, 2012). We have studied the role of IL-33/ST2 signaling in murine cytomegalovirus (MCMV) infection and found that ST2-deficient mice had weaker NK cell and CTL responses to MCMV than control wild-type mice. These results suggest that IL-33 signals through ST2 receptor to amplify NK cell and effector T cell responses to virus infection. In spite of this, ST2-deficient mice showed normal MCMV control, indicating alternative mechanism induced in absence of ST2. Moreover, newborn ST2-deficient mice infected with MCMV showed much milder liver pathology compared to control mice, suggesting involvement of ST2 signaling in inflammatory response.

IL-33; ST2; MCMV; CD8 response

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