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NIH Research Festival

September 16 – 18, 2015

A role for S1P4 receptor function in the modulation of immune responses and IgE production in vivo

Thursday, September 17, 2015 – Poster Session III
3:30 – 5:00 p.m.

FAES Terrace

NIAID

IMMUNO-20

Authors

  • JM Kulinski
  • AC Poholek
  • A Olivera

Abstract

Sphingosine 1 phosphate (S1P) is a bioactive sphingolipid that influences a variety of cellular functions and disease processes including inflammation largely through stimulation of a combination of specific S1P-binding G protein-coupled receptors (S1P1-5). While signaling through S1P1 and S1P2 receptors has been demonstrated to regulate key processes associated with the development of allergic disease, little is known about the contributions from other S1P receptors. Mice deficient in the S1P4 receptor exhibit significantly elevated serum levels of IgE and a high propensity towards hyperesponsiveness in models of allergic inflammation. We found that S1P4 receptor deficient mice have a significantly higher frequency of germinal center B cells in the spleen compared to wt littermates following immunization. To assess the involvement of antigen-specific TFH cells in supporting this process, we generated a S1P4 deficient mouse strain expressing a transgenic T cell receptor specific for OVA peptide (OT-II). Splenocytes from these mice were adoptively transferred to wild type mice prior to immunization with OVA. A significantly higher proportion of transferred S1P4 deficient, OVA-specific TFH cells were present in the spleen of immunized mice when compared to mice that had received OVA-specific WT cells prior to immunization. Furthermore, we have found that global S1P4 receptor deficiency in mice also increases the expression of a basophil activation marker that correlates with the ability of these cells to support IgE production. Our findings suggest previously uncharacterized roles for the S1P4 receptor in regulating class-switching to IgE by influencing the accumulation of key immune cells in lymphoid tissue.

Scientific Focus Area: Immunology

This page was last updated on Friday, March 26, 2021

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