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TGF-β production by eosinophils drives the expansion of peripherally induced neuropilin - RORγt + regulatory T-cells during bacterial and allergen challenge


Fallegger, Angela; Priola, Martina; Artola-Borán, Mariela; Núñez, Nicolás Gonzalo; Wild, Sebastian; Gurtner, Alessandra; Becher, Burkhard; Yousefi, Shida; Simon, Hans-Uwe; Arnold, Isabelle C; Müller, Anne (2022). TGF-β production by eosinophils drives the expansion of peripherally induced neuropilin - RORγt + regulatory T-cells during bacterial and allergen challenge. Mucosal Immunology, 15(3):504-514.

Abstract

Eosinophils are best known for their effector functions in settings of parasitic infection or allergen challenge, but have also increasingly been implicated in immune regulation at mucosal sites. Here, we show using bacterial infection and antigen challenge models that extrathymic Foxp3+ regulatory T-cells that arise de novo in the context of bacterial infection require an intact eosinophil compartment. Mouse strains with a constitutive or conditional eosinophil deficiency, or with an eosinophil-specific ablation of Tgfb, lack bacterially induced neuropilin-negative, RORγt-positive gastrointestinal Treg populations in models of Helicobacter pylori, Helicobacter hepaticus and Citrobacter rodentium infection, as well as in the steady state colon and upon oral ovalbumin challenge. Treg priming in lymph nodes appears not to be impaired. Eosinophil-dependent tissue-resident Tregs express CTLA4, ICOS, CD39 and T-bet in addition to RORγt. Eosinophils reside in close proximity to Tregs in infected tissues, and specifically induce the expansion of newly formed Tregs, but not conventional T-cells in vivo and in vitro. TGF-β expression in eosinophils is induced by bacterial contact and during allergen exposure. Specific Tgfb ablation in eosinophils and the associated Treg defects result in excessive T-cell responses in the examined Th2- but not Th1-polarized settings.

Abstract

Eosinophils are best known for their effector functions in settings of parasitic infection or allergen challenge, but have also increasingly been implicated in immune regulation at mucosal sites. Here, we show using bacterial infection and antigen challenge models that extrathymic Foxp3+ regulatory T-cells that arise de novo in the context of bacterial infection require an intact eosinophil compartment. Mouse strains with a constitutive or conditional eosinophil deficiency, or with an eosinophil-specific ablation of Tgfb, lack bacterially induced neuropilin-negative, RORγt-positive gastrointestinal Treg populations in models of Helicobacter pylori, Helicobacter hepaticus and Citrobacter rodentium infection, as well as in the steady state colon and upon oral ovalbumin challenge. Treg priming in lymph nodes appears not to be impaired. Eosinophil-dependent tissue-resident Tregs express CTLA4, ICOS, CD39 and T-bet in addition to RORγt. Eosinophils reside in close proximity to Tregs in infected tissues, and specifically induce the expansion of newly formed Tregs, but not conventional T-cells in vivo and in vitro. TGF-β expression in eosinophils is induced by bacterial contact and during allergen exposure. Specific Tgfb ablation in eosinophils and the associated Treg defects result in excessive T-cell responses in the examined Th2- but not Th1-polarized settings.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research

04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Language:English
Date:March 2022
Deposited On:14 Jun 2022 09:24
Last Modified:27 Feb 2024 02:42
Publisher:Nature Publishing Group
ISSN:1933-0219
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41385-022-00484-0
PubMed ID:35169233
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)