抄録
Mast cells (MCs) are highly plastic cells whose phenotype is modulated by local signals. We explored the hypothesis that the mesenchymal cytokine IL-33 enables participation of synovial MCs in murine K/BxN arthritis by promoting activation via immune complexes. Compared to WT controls, mice lacking the IL-33 receptor ST2 exhibited attenuated arthritis. Whereas participation of MCs in this model is mediated via FcgRIII, we pre-incubated MCs with IL-33 and found a marked increase in IgG-driven production of mediators including IL-1β and CXCL2. Besides, WT but not ST2-null MCs induced fibroblasts to express IL-33, constituting a positive feedback circuit. Together, these findings confirm a novel role for IL 33 as an amplifier of immune complex-mediated inflammation and define a MC-fibroblast amplification loop dependent on IL-33 and its receptor.
