IL-1 receptor accessory protein is essential for IL-33-induced activation of T lymphocytes and mast cells.
Lack of the IL-1 receptor accessory protein (IL-1RAcP) abrogates responses to IL-33 and IL-1 in the mouse thymoma clone EL-4 D6/76 cells. Reconstitution with full-length IL-1RAcP is sufficient to restore responsiveness to IL-33 and IL-1. IL-33 activates IL-1 receptor-associated kinase-1, cJun-N-terminal kinase, and the NF-kappaB pathway in an IL-1RAcP-dependent manner and results in IL-2 release. IL-33 is able to induce the release of proinflammatory cytokines in bone marrow-derived (BMD) 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. Blocking of murine IL-1RAcP with the neutralizing antibody 4C5 inhibits response of mouse thymoma cells and BMD mast cells to IL-33. The interaction of either membrane-bound or soluble forms of IL-1RAcP and IL-33Ralpha-chain depends on the presence of IL-33, as demonstrated by coimmunoprecipitation assays. These data demonstrate that IL-1RAcP is indispensable for IL-33 signaling. Furthermore, they suggest that IL-1RAcP is used by more than one alpha-chain of the IL-1 receptor family and thus may resemble a common beta-chain of that family.
Ali
Shafaqat
S
Immunology FB08, Justus-Liebig-University Giessen, Winchesterstrasse 2, D-35394 Giessen, Germany.
Huber
Michael
M
Kollewe
Christian
C
Bischoff
Stephan C
SC
Falk
Werner
W
Martin
Michael U
MU
D000818:Animals; D002460:Cell Line; D006801:Humans; D053577:Interleukin-1 Receptor Accessory Protein / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
C507767:Il1rap protein, mouse; C506535:Il33 protein, mouse; D053577:Interleukin-1 Receptor Accessory Protein; D000067596:Interleukin-33; D007378:Interleukins