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Hematopoietic prostaglandin D synthase defines a subset of "super-effector" Th2 cells with enhanced function and an innate lymphoid program

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)

NIAID

IMMUNO-19

Authors

  • A. Mitson-Salazar
  • D. Wansley
  • C. Prussin

Abstract

Th2 cells express IL-4, IL-5 and IL-13 and play a fundamental role in allergy and asthma pathogenesis. We have previously characterized two human Th2 subpopulations, IL-5- and IL-5+ Th2 cells, the latter being a highly differentiated subset of Th2 cells. Using microarray transcription profiling, we identified hematopoietic prostaglandin D synthase (hPGDS) as the most highly up-regulated gene expressed by IL-5+ Th2 cells. We thus used a monoclonal antibody to hPGDS to identify and characterize IL-5+ Th2 cells. hPGDS identified an IL-5bright Th2 subpopulation that was present in eosinophilic gastrointestinal disorder (EGID) subjects, but not healthy controls. The frequency of hPGDS+ Th2 cells was highly correlated to blood eosinophil count (r = 0.96). hPGDS+ Th2 cells expressed HLA-DR, PD-1, and TSLP-R, but not CD27 or IL-7R, consistent with highly differentiated effector cells. In response to activation with a variety of cytokines (IL-2, IL-25, IL-33, TSLP), hPGDS+ Th2 cells produced more IL-5 and IL-13 than did hPGDS- Th2. In this work we have characterized a novel subpopulation of "super-effector" Th2 cells that have enhanced effector function and are highly correlated to eosinophilic disease. These data strongly support a role for hPGDS+ Th2 cells in the pathogenesis of allergic inflammation.

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