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CD103 integrin identifies a high IL-10-producing FoxP3 + regulatory T cell population suppressing allergic airway inflammation
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  • Sofia Tagkareli,
  • Maria Salagianni,
  • Ioanna Galani,
  • Maria Manioudaki,
  • Eleftherios Pavlos,
  • Kalliopi Thanopoulou,
  • Evangelos Andreakos
Sofia Tagkareli
Novartis Institutes for BioMedical Research Shanghai

Corresponding Author:[email protected]

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Maria Salagianni
Novartis Institutes for BioMedical Research Shanghai
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Ioanna Galani
Novartis Institutes for BioMedical Research Shanghai
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Maria Manioudaki
Novartis Institutes for BioMedical Research Shanghai
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Eleftherios Pavlos
Novartis Institutes for BioMedical Research Shanghai
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Kalliopi Thanopoulou
Novartis Institutes for BioMedical Research Shanghai
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Evangelos Andreakos
Novartis Institutes for BioMedical Research Shanghai
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Abstract

Background: Although FoxP3 + regulatory T (Treg) cells constitute a highly heterogeneous population, with different regulatory potential depending on the disease context, distinct subsets or phenotypes remain poorly defined. This hampers the development of immunotherapy for allergic and autoimmune disorders. Objective: This study aimed at characterizing distinct FoxP3 + Treg subpopulations involved in the suppression of Th2-mediated allergic inflammation in the lung. Methods: We used an established mouse model of allergic airway disease based on ovalbumin sensitization and challenge to analyze FoxP3 + Tregs during the induction and resolution of inflammation, and identify markers that distinguish their most suppressive phenotypes. We also developed a new knock-in mouse model ( Foxp3creCd103dtr) enabling the specific ablation of CD103 +FoxP3 + Tregs for functional studies. Results: We found that during resolution of allergic airway inflammation in mice >50% of FoxP3 + Treg cells expressed the integrin CD103 which marks FoxP3 + Treg cells of high IL-10 production, increased expression of immunoregulatory molecules such as KLRG1, ICOS and CD127, and enhanced suppressive capacity for Th2-mediated inflammatory responses. CD103 +FoxP3 + Tregs were essential for keeping allergic inflammation under control as their specific depletion in Foxp3creCd103dtr mice lead to severe alveocapillary damage, eosinophilic pneumonia, and markedly reduced lifespan of the animals. Conversely, adoptive transfer of CD103 +FoxP3 + Tregs effectively treated disease, attenuating Th2 responses and allergic inflammation in an IL-10-dependent manner. Conclusion: Our study identifies a novel regulatory T cell population, defined by CD103 expression, programmed to prevent exuberant type 2 inflammation and keep homeostasis in the respiratory tract under control. This has important therapeutic implications.
10 Aug 2021Submitted to Allergy
10 Aug 2021Submission Checks Completed
10 Aug 2021Assigned to Editor
11 Aug 2021Reviewer(s) Assigned
23 Aug 2021Review(s) Completed, Editorial Evaluation Pending
25 Aug 2021Editorial Decision: Revise Minor
11 Sep 20211st Revision Received
13 Sep 2021Submission Checks Completed
13 Sep 2021Assigned to Editor
17 Sep 2021Reviewer(s) Assigned
01 Oct 2021Review(s) Completed, Editorial Evaluation Pending
03 Oct 2021Editorial Decision: Accept
Apr 2022Published in Allergy volume 77 issue 4 on pages 1150-1164. 10.1111/all.15144