IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex

@article{Chackerian2007IL1RA,
  title={IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex},
  author={Alissa A. Chackerian and Elizabeth R. Oldham and Erin E. Murphy and Jochen Schmitz and Stefan Pflanz and Robert A. Kastelein},
  journal={The Journal of Immunology},
  year={2007},
  volume={179},
  pages={2551 - 2555}
}
IL-33 (IL-1F11) is a recently described member of the IL-1 family of cytokines that stimulates the generation of cells, cytokines, and Igs characteristic of a type 2 immune response. IL-33 mediates signal transduction through ST2, a receptor expressed on Th2 and mast cells. In this study, we demonstrate that IL-33 and ST2 form a complex with IL-1R accessory protein (IL-1RAcP), a signaling receptor subunit that is also a member of the IL-1R complex. Additionally, IL-1RAcP is required for IL-33… 
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The IL-1 receptor accessory protein (AcP) is required for IL-33 signaling and soluble AcP enhances the ability of soluble ST2 to inhibit IL-33.
Characterization of Interleukin-33 and the Il-33 Receptor Complex
IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells
TLDR
IL-33 is able to induce the release of proinflammatory cytokines in bone marrow-derived mast cells, indicating that IL-33 may have a proinflammatory potential like its relatives IL-1 and IL-18, in addition to its Th2-skewing properties in the adaptive response described previously.
The inhibitory function of Fc-ST2 depends on cell type; IL-1RAcP and ST2 are necessary but insufficient for IL-33 activity
TLDR
The results suggest that an additional receptor component may participate in the biological activity of IL- 33, and suggest that IL-1RAcP and ST2 are necessary but insufficient for IL-33 activity.
Reconstitution of ST2 (IL-1R4) specific for IL-33 activity; no suppression by IL-1Ra though a common chain IL-1R3 (IL-1RAcP) shared with IL-1.
The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1
TLDR
It is reported here that full-length IL-331–270 is active and that processing by caspase-1 results in IL-33 inactivation, rather than activation, and that IL-34 may function, similarly to the prototypical alarmins HMGB1 and IL-1α, as an endogenous danger signal to alert cells of the innate immune system of tissue damage during trauma or infection.
Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes.
NUCLEAR FUNCTION AND RELEASE OF IL-33
TLDR
Interleukin-33 is now recognized as the specific ligand for the orphan IL-1 receptor familymember ST2 and to be involved in polarization of T cells towards T helper 2-cell phenotype and inactivation of mast cells, basophils, eosinophils and natural killer cells.
Special aspects of interleukin-33 and the IL-33 receptor complex.
Identification of Constitutively Active Interleukin 33 (IL-33) Splice Variant*
TLDR
The existence of constitutively active spIL-33 suggests that the biological activity of IL-33 could be triggered by diverse stimulations during immune responses, and further investigation of the spIL/IL-1F11 expression pattern may contribute to understanding the involvement of Il-33 in inflammatory disorders.
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