| Literature DB >> 19234154 |
Katarzyna Bulek1, Shadi Swaidani, Jinzhong Qin, Yi Lu, Muhammet F Gulen, Tomasz Herjan, Booki Min, Robert A Kastelein, Mark Aronica, Magdalena Kosz-Vnenchak, Xiaoxia Li.
Abstract
A novel cytokine IL-33, an IL-1 family member, signals via ST2 receptor and promotes Th2 responses, through the activation of NF-kappaB and MAP kinases. Previous studies reported that single Ig IL-1R-related molecule (SIGIRR)/Toll IL-1R8 acts as negative regulator for TLR-IL-1R-mediated signaling. We now found that SIGIRR formed a complex with ST2 upon IL-33 stimulation and specifically inhibited IL-33/ST2-mediated signaling in cell culture model. Furthermore, IL-33-induced Th2 response was enhanced in SIGIRR-deficient mice compared with that in wild-type control mice, suggesting a negative regulatory role of SIGIRR in IL-33/ST2 signaling in vivo. Similar to ST2, SIGIRR was highly expressed in in vitro polarized Th2 cells, but not Th1 cells. SIGIRR-deficient Th2 cells produce higher levels of Th2 cytokines, including IL-5, IL-4, and IL-13, than that in wild-type cells. Moreover, SIGIRR-deficient mice developed stronger Th2 immune response in OVA-challenged asthma model. Taken together, our results suggest that SIGIRR plays an important role in the regulation of Th2 response in vivo, possibly through its impact on IL-33-ST2-mediated signaling.Entities:
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Year: 2009 PMID： 19234154 PMCID： PMC2891188 DOI： 10.4049/jimmunol.0802729
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422