UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

FOXP3(+) Tregs require WASP to restrain Th2-mediated food allergy

Lexmond, WS; Goettel, JA; Lyons, JJ; Jacobse, J; Deken, MM; Lawrence, MG; DiMaggio, TH; ... Fiebiger, E; + view all (2016) FOXP3(+) Tregs require WASP to restrain Th2-mediated food allergy. Journal of Clinical Investigation , 126 (10) pp. 4030-4044. 10.1172/JCI85129. Green open access

[thumbnail of Thrasher_Lexmond WAS 100215.pdf]
Preview
Text
Thrasher_Lexmond WAS 100215.pdf - Accepted Version

Download (263kB) | Preview
[thumbnail of Lexmond Legends and Figures 093015.pdf]
Preview
Text
Lexmond Legends and Figures 093015.pdf - Accepted Version

Download (3MB) | Preview

Abstract

In addition to the infectious consequences of immunodeficiency, patients with Wiskott-Aldrich syndrome (WAS) often suffer from poorly understood exaggerated immune responses that result in autoimmunity and elevated levels of serum IgE. Here, we have shown that WAS patients and mice deficient in WAS protein (WASP) frequently develop IgE-mediated reactions to common food allergens. WASP-deficient animals displayed an adjuvant-free IgE-sensitization to chow antigens that was most pronounced for wheat and soy and occurred under specific pathogen–free as well as germ-free housing conditions. Conditional deletion of Was in FOXP3+ Tregs resulted in more severe Th2-type intestinal inflammation than that observed in mice with global WASP deficiency, indicating that allergic responses to food allergens are dependent upon loss of WASP expression in this immune compartment. While WASP-deficient Tregs efficiently contained Th1- and Th17-type effector differentiation in vivo, they failed to restrain Th2 effector responses that drive allergic intestinal inflammation. Loss of WASP was phenotypically associated with increased GATA3 expression in effector memory FOXP3+ Tregs, but not in naive-like FOXP3+ Tregs, an effect that occurred independently of increased IL-4 signaling. Our results reveal a Treg-specific role for WASP that is required for prevention of Th2 effector cell differentiation and allergic sensitization to dietary antigens.

Type: Article
Title: FOXP3(+) Tregs require WASP to restrain Th2-mediated food allergy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/JCI85129
Publisher version: http://dx.doi.org/10.1172/JCI85129
Language: English
Additional information: Copyright © 2016 American Society for Clinical Investigation
Keywords: Science & Technology, Life Sciences & Biomedicine, Medicine, Research & Experimental, Research & Experimental Medicine, Wiskott-Aldrich-Syndrome, Regulatory T-Cells, Syndrome Protein Wasp, Mast-Cells, In-Vivo, Antigen Receptor, Type-2 Immunity, National-Health, Ige Levels, Mice
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1532844
Downloads since deposit
167Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item