Interleukin-33 promotes the proliferation of mouse mast cells through ST2/MyD88 and p38 MAPK-dependent and Kit-independent pathways.

Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is emerging as a new modulator of immune and inflammatory responses. Although IL-33 and its associated receptor ST2 are reportedly expressed in mast cells (MCs), the precise role of IL-33 in modulating MC function has not been determined. In the present studies, we explored IL-33 effects on MCs in vivo and in vitro. IL-33 increased the number of peritoneal and skin MCs in vivo. IL-33 also resulted in increased proliferation of MCs in vitro, as explored by WST assay. Cell cycle analysis further confirmed this result by showing increased G2 cell populations in MCs stimulated with IL-33. We found that IL-33-mediated MC proliferation requires ST2 and MyD88, is independent of Kit, and is mediated through a p38 MAPK-dependent pathway. IL-33 did not induce degranulation and was not cytotoxic for MCs. This novel mechanism for increasing MC proliferation and numbers further defines the role of IL-33 in MC-dependent diseases including allergies and may help to develop novel approaches for the treatment of these disorders.