[PDF][PDF] IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines

J Schmitz, A Owyang, E Oldham, Y Song, E Murphy… - Immunity, 2005 - cell.com
J Schmitz, A Owyang, E Oldham, Y Song, E Murphy, TK McClanahan, G Zurawski…
Immunity, 2005cell.com
Cytokines of the interleukin-1 (IL-1) family, such as IL-1α/β and IL-18, have important
functions in host defense, immune regulation, and inflammation. Insight into their biological
functions has led to novel therapeutic approaches to treat human inflammatory diseases.
Within the IL-1 family, IL-1α/β, IL-1Ra, and IL-18 have been matched to their respective
receptor complexes and have been shown to have distinct biological functions. The most
prominent orphan IL-1 receptor is ST2. This receptor has been described as a negative …
Summary
Cytokines of the interleukin-1 (IL-1) family, such as IL-1α/β and IL-18, have important functions in host defense, immune regulation, and inflammation. Insight into their biological functions has led to novel therapeutic approaches to treat human inflammatory diseases. Within the IL-1 family, IL-1α/β, IL-1Ra, and IL-18 have been matched to their respective receptor complexes and have been shown to have distinct biological functions. The most prominent orphan IL-1 receptor is ST2. This receptor has been described as a negative regulator of Toll-like receptor-IL-1 receptor signaling, but it also functions as an important effector molecule of T helper type 2 responses. We report a member of the IL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST2, activates NF-κB and MAP kinases, and drives production of TH2-associated cytokines from in vitro polarized TH2 cells. In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs.
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