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The Effects of Altered TGFβ Signaling on Human T Follicular Helper Cell Development and Function

Thursday, September 13, 2018 — Poster Session III

12:00 p.m. – 1:30 p.m.
FAES Terrace
NIAID
IMMUNO-25

Authors

  • Z Schmiechen
  • K Weissler
  • K Laky
  • P Guerrerio

Abstract

T follicular helper cells (Tfh cells) are a subset of CD4+ T cells that play a crucial role in the development of memory B cells and plasma cells, in part through their expression of IL-4 and IL-21. T follicular regulatory (Tfr) cells oppose Tfh cells and suppress humoral immune responses. Patients with Loeys-Dietz Syndrome (LDS) type 1 and 2 have an autosomal dominant mutation in the genes encoding TGFβ Receptor 1 or 2, respectively, and have a strong predisposition to develop allergic diseases. We hypothesized that Tfh cells could contribute to increased IgE-mediated allergic phenotypes in LDS. Comparing a cohort of pediatric LDS patients with age-matched healthy volunteers, we found that that LDS patients have significantly higher levels of serum IgE and IgG and lower levels of IgM. Congruently, LDS patients have an increased frequency of memory T, Tfh, and Th2 cells, and a significantly lower frequency of Tfr cells. Experiments are underway to examine whether Tfh cells from LDS patients induce altered B cell differentiation, and how dysregulation of TGFβ signaling affects the differentiation of Tfh cells. Collectively, our data suggest that LDS mutations alter the development and function of Tfh cells in a manner that promotes IgE-mediated disease.

Category: Immunology