The role of MyD88 in the synergy between FcϵR1, TLR4 and ST2 in mast cells. (91.5)

Abstract

Abstract Mast cells are well established as important effector cells in allergic reactions. Cross-linking of the high affinity IgE receptor (FcϵRI) on mast cells by allergen causes degranulation leading to the release and generation of a variety of inflammatory mediators. IL-33 and lipopolysaccharide (LPS) are members of the IL-1 family that use MyD88 as an adaptor molecule for signalling. Alone, IL-33 and LPS are unable to cause mast cell degranulation but they can induce cytokine generation. In addition, IL-33 and LPS synergise with antigen/IgE for cytokine production in mast cells. IL-33 and LPS-induced cytokine production was abolished in MyD88-deficient (MyD88-/-) bone marrow-derived mast cells (BMMCs). Surprisingly, antigen/IgE-mediated cytokine production was also substantially reduced in MyD88-/- BMMCs. However, MyD88 had no effect on FcϵRI expression, calcium mobilisation or degranulation. The synergy between IL-33 and antigen/IgE in IL-13 production by BMMCs was shown to be MyD88-dependent. Similarly, MyD88 was required for cytokine production in LPS and antigen/IgE stimulated BMMCs. The synergy between LPS and antigen/IgE for cytokine generation also required p38 MAP kinase activation. These findings suggest that MyD88 signalling in mast cells could provide a novel target to modulate allergic diseases.