A role for S1P4 receptor expression in the modulation of immune responses and mast cell function

Authors

• JM Kulinski
• A Olivera
• DD Metcalfe

Abstract

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that can influence a variety of cellular functions and disease processes by signaling through a combination of S1P-binding G protein-coupled receptors (S1P1-5). While signaling through S1P1 and S1P2 receptors has been demonstrated to regulate key processes in mast cells associated with the development of allergic disease, little is known about contributions from the closely related S1P4 receptor also expressed in mast cells and other immune cells. Upon exposure to allergen, immune cells including mast cells, basophils, T lymphocytes and B lymphocytes are recruited to specific sites within lymphoid tissue and S1P signaling has been demonstrated to play a role in this process. We and others have shown that mice deficient in the S1P4 receptor exhibit significantly elevated serum levels of IgE and a high propensity towards hyperesponsiveness in models of TH2-driven inflammation. In this study, we set out to understand the mechanism by which S1P4 receptor expression regulates allergic inflammation. We examined the influence of S1P4 expression during immune responses in vivo as well as in the regulation of mast cell differentiation and function in vitro. Our data suggest a previously uncharacterized and complex role for the S1P4 receptor in regulating immune function and mast cell responses to antigen-mediated activation. The enhanced allergic inflammatory responses in S1P4 deficient mice may be related in part to this modulatory effect.

Scientific Focus Area: Immunology

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