Abstracts (complete list) - Wissenschaft Online

Shafaqat Ali, Michael Huber, Christian Kollewe, Werner Falk, Michael U. Martin
The Interleukin-1 Receptor Accessory Protein is essential for
Interleukin-33 induced activation of T cells and mast cells
Interleukin-33 (IL-33) is a novel member of the IL-1 family of cytokines. It binds to the
IL-33 receptor alpha chain, formerly known as ST2/T1, which is a member of the IL-1
receptor family (Schmitz et al. Immunity 2005, 23, 479-490). Here we show that lack of
the Interleukin-1 receptor accessory protein (IL-1RAcP) abrogates responses to IL-33 in
the mouse thymoma clone EL-4 D6/76. Reconstitution with full length IL-1RAcP, but not
with a C-terminally truncated version lacking the TIR-domain, is sufficient to restore
responsiveness to IL-33. Blocking of murine IL-1RAcP with the neutralizing antibody
4C5 inhibits response of mouse thymoma cells and bone marrow-derived mouse mast
cells to IL-33 with respect to cytokine production. IL-33 activates IL-1 receptor
associated kinase (IRAK-1), the stress kinases p38 and c-Jun N-terminal kinase, and
the NF-kappaB pathway in an IL-1RAcP dependent manner. IL-33 is able to induce the
production and release of pro-inflammatory cytokines in transiently transfected cells
and bone marrow-derived mast cells, indicating that IL-33 may have a proinflammatory
potential (in the innate response) like its relatives IL-1 and IL-18 besides
of its Th2-skewing properties in the adaptive response described previously. The
interaction of IL-1RAcP and IL-33Ralpha-chain is dependent on IL-33 as demonstrated
in co-immunoprecipitation assays.
We conclude that IL-1RAcP is required as co-receptor in the signalling IL-33 receptor
complex. Thus IL-1RAcP is utilized by more than one beta-chain of the IL-1 receptor
family and may resemble a common beta-chain of the IL-1 receptor family.