Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Divergent T follicular helper cell requirement for IgA and IgE production to peanut during allergic sensitization

Zhang, Biyan ; Liu, Elise ; Gertie, Jake A ; Joseph, Julie ; Xu, Lan ; Pinker, Elisha Y ; Waizman, Daniel A ; Catanzaro, Jason ; Hamza, Kedir Hussen LU and Lahl, Katharina LU , et al. (2020) In Science Immunology 5(47).
Abstract

Immunoglobulin A (IgA) is the dominant antibody isotype in the gut and has been shown to regulate microbiota. Mucosal IgA is also widely believed to prevent food allergens from penetrating the gut lining. Even though recent work has elucidated how bacteria-reactive IgA is induced, little is known about how IgA to food antigens is regulated. Although IgA is presumed to be induced in a healthy gut at steady state via dietary exposure, our data do not support this premise. We found that daily food exposure only induced low-level, cross-reactive IgA in a minority of mice. In contrast, induction of significant levels of peanut-specific IgA strictly required a mucosal adjuvant. Although induction of peanut-specific IgA required T cells and... (More)

Immunoglobulin A (IgA) is the dominant antibody isotype in the gut and has been shown to regulate microbiota. Mucosal IgA is also widely believed to prevent food allergens from penetrating the gut lining. Even though recent work has elucidated how bacteria-reactive IgA is induced, little is known about how IgA to food antigens is regulated. Although IgA is presumed to be induced in a healthy gut at steady state via dietary exposure, our data do not support this premise. We found that daily food exposure only induced low-level, cross-reactive IgA in a minority of mice. In contrast, induction of significant levels of peanut-specific IgA strictly required a mucosal adjuvant. Although induction of peanut-specific IgA required T cells and CD40L, it was T follicular helper (TFH) cell, germinal center, and T follicular regulatory (TFR) cell-independent. In contrast, IgG1 and IgE production to peanut required TFH cells. These data suggest an alternative paradigm in which the cellular mechanism of IgA production to food antigens is distinct from IgE and IgG1. We developed an equivalent assay to study this process in stool samples from healthy, nonallergic humans, which revealed substantial levels of peanut-specific IgA that were stable over time. Similar to mice, patients with loss of CD40L function had impaired titers of gut peanut-specific IgA. This work challenges two widely believed but untested paradigms about antibody production to dietary antigens: (i) the steady state/tolerogenic response to food antigens includes IgA production and (ii) TFH cells drive food-specific gut IgA.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Immunology
volume
5
issue
47
article number
eaay2754
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:32385053
  • scopus:85084720929
ISSN
2470-9468
DOI
10.1126/sciimmunol.aay2754
language
English
LU publication?
yes
additional info
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
id
a6875e4b-63bf-471e-aa27-1fb8517d63c1
date added to LUP
2020-05-18 21:29:38
date last changed
2024-06-13 16:31:21
@article{a6875e4b-63bf-471e-aa27-1fb8517d63c1,
  abstract     = {{<p>Immunoglobulin A (IgA) is the dominant antibody isotype in the gut and has been shown to regulate microbiota. Mucosal IgA is also widely believed to prevent food allergens from penetrating the gut lining. Even though recent work has elucidated how bacteria-reactive IgA is induced, little is known about how IgA to food antigens is regulated. Although IgA is presumed to be induced in a healthy gut at steady state via dietary exposure, our data do not support this premise. We found that daily food exposure only induced low-level, cross-reactive IgA in a minority of mice. In contrast, induction of significant levels of peanut-specific IgA strictly required a mucosal adjuvant. Although induction of peanut-specific IgA required T cells and CD40L, it was T follicular helper (TFH) cell, germinal center, and T follicular regulatory (TFR) cell-independent. In contrast, IgG1 and IgE production to peanut required TFH cells. These data suggest an alternative paradigm in which the cellular mechanism of IgA production to food antigens is distinct from IgE and IgG1. We developed an equivalent assay to study this process in stool samples from healthy, nonallergic humans, which revealed substantial levels of peanut-specific IgA that were stable over time. Similar to mice, patients with loss of CD40L function had impaired titers of gut peanut-specific IgA. This work challenges two widely believed but untested paradigms about antibody production to dietary antigens: (i) the steady state/tolerogenic response to food antigens includes IgA production and (ii) TFH cells drive food-specific gut IgA.</p>}},
  author       = {{Zhang, Biyan and Liu, Elise and Gertie, Jake A and Joseph, Julie and Xu, Lan and Pinker, Elisha Y and Waizman, Daniel A and Catanzaro, Jason and Hamza, Kedir Hussen and Lahl, Katharina and Gowthaman, Uthaman and Eisenbarth, Stephanie C}},
  issn         = {{2470-9468}},
  language     = {{eng}},
  month        = {{05}},
  number       = {{47}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Immunology}},
  title        = {{Divergent T follicular helper cell requirement for IgA and IgE production to peanut during allergic sensitization}},
  url          = {{http://dx.doi.org/10.1126/sciimmunol.aay2754}},
  doi          = {{10.1126/sciimmunol.aay2754}},
  volume       = {{5}},
  year         = {{2020}},
}