Identification of a T follicular helper cell subset that drives anaphylactic IgE

Uthaman Gowthaman, Jennifer S. Chen, Biyan Zhang, William F. Flynn, Yisi Lu, Wenzhi Song, Julie Joseph, Jake A. Gertie, Lan Xu, Magalie A. Collet, Jessica D.S. Grassmann, Tregony Simoneau, David Chiang, M. Cecilia Berin, Joseph E. Craft, Jason S. Weinstein, Adam Williams, Stephanie C. Eisenbarth

Research output: Contribution to journalArticlepeer-review

Abstract

Cross-linking of high-affinity immunoglobulin E (IgE) results in the life-threatening allergic reaction anaphylaxis. Yet the cellular mechanisms that induce B cells to produce IgE in response to allergens remain poorly understood. T follicular helper (TFH) cells direct the affinity and isotype of antibodies produced by B cells. Although TFH cell–derived interleukin-4 (IL-4) is necessary for IgE production, it is not sufficient. We report a rare population of IL-13–producing TFH cells present in mice and humans with IgE to allergens, but not when allergen-specific IgE was absent or only low-affinity. These “TFH13” cells have an unusual cytokine profile (IL-13hiIL-4hiIL-5hiIL-21lo) and coexpress the transcription factors BCL6 and GATA3. TFH13 cells are required for production of high- but not low-affinity IgE and subsequent allergen-induced anaphylaxis. Blocking TFH13 cells may represent an alternative therapeutic target to ameliorate anaphylaxis.

Original languageEnglish (US)
Article numberaaw6433
JournalScience Robotics
Volume4
Issue number34
DOIs
StatePublished - Sep 18 2019

ASJC Scopus subject areas

  • Mechanical Engineering
  • Computer Science Applications
  • Control and Optimization
  • Artificial Intelligence

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