ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance

Nature Immunol. 2004; 5: 380-387

Speaker: 張美蘭                            Commentator: 葉才明 老師

Date: 2004/05/05 14:00-15:00                  Place: Room 601

Abstract :

    The TIR (Toll-interleukin 1 receptor) superfamily possesses the conserved protein sequence in the cytosolic domain. Signaling through TIR members leads to NFkB activation to promote a cascade of proinflammatory cytokines production. ST2, a member of the TIR family, is expressed by fibroblasts, mast cells, and Th2, but not Th1 cells. ST2 is a stable marker distinguishing Th2 from Th1 cells and is also associated with Th2 effector functions. ST2 was unable to activate NFkB, resulted in suppressing proinflammatory cytokine production. LPS-induced mortality in vivo is blocked by ST2. ST2 down-regulates the expression of IL-1RI, TLR4 (Toll-like receptor 4), TLR2 and TLR9; but not poly(I:C) induced TLR3 signaling. The inhibitory effect of ST2 was achieved by the sequestration of the adaptor proteins, MyD88 and Mal. ST2 expression plays a role in the development of Th2-like cytokine response and indicates that effector function are inhibited in its absence. ST2 has a key function in endotoxin tolerance. Blockade of endogenous ST2 through administration of anti-ST2 Ab exacerbated the toxic effects of LPS. So ST2 may be a potential therapeutic strategy for inflammatory

diseases.

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