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IL-10-modulated dendritic cells from birch pollen- and hazelnut-allergic patients facilitate Treg-mediated allergen-specific and cross-reactive tolerance
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  • Patricia Vanessa Heinl,
  • Edith Graulich,
  • Benno Weigmann,
  • Andrea Wangorsch,
  • Robert Ose,
  • Iris Bellinghausen,
  • Stephan Scheurer,
  • Stefan Vieths,
  • Joachim Saloga,
  • Kerstin Steinbrink
Patricia Vanessa Heinl
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz Hautklinik und Poliklinik
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Edith Graulich
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz Hautklinik und Poliklinik
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Benno Weigmann
Universitatsklinikum Erlangen
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Andrea Wangorsch
Paul-Ehrlich-Institut
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Robert Ose
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz Hautklinik und Poliklinik
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Iris Bellinghausen
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz Hautklinik und Poliklinik
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Stephan Scheurer
Paul-Ehrlich-Institut
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Stefan Vieths
Paul-Ehrlich-Institut
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Joachim Saloga
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz Hautklinik und Poliklinik
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Kerstin Steinbrink
Universitatsmedizin der Johannes Gutenberg-Universitat Mainz Hautklinik und Poliklinik

Corresponding Author:[email protected]

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Abstract

Background Approximately 70 % of individuals allergic to birch pollen (Bet v 1.01 [Bet]) develop a secondary food allergy (e.g. hazelnut: Cor a 1.04 [Cor]), due to allergen cross-reactivity. However, standard immunotherapy for type I allergies often does not improve the food allergy sufficiently. We analyzed the allergen-specific and cross-reactive suppressive capacity of primary human regulatory T cells (Treg) induced by autologous IL-10-modulated dendritic cells (IL-10 DC) in vitro and in vivo. Methods CD4 + T cells of patients with birch pollen and associated hazelnut allergies were differentiated into Bet-specific or non-specific induced Treg (iTreg). After Bet- or Cor- specific restimulation the phenotype, proliferation and suppressive capacity of iTreg subsets were analyzed. iTreg function was further investigated in humanized mouse models of airway and intestinal allergy, generated by engraftment of peripheral blood mononuclear cells from allergic donors into immunodeficient animals. Results After IL-10 DC priming and allergen-specific restimulation (Bet or Cor) non-specific control iTreg remained anergic, whereas Bet-specific iTreg proliferated extensively and exhibited a regulatory phenotype (enhanced expression of CTLA-4, PD-1, TNFR2, IL-10). Accordingly, activated Bet-specific iTreg displayed a high capacity to suppress Bet- and Cor-induced responder T H2 cell responses in vitro, indicating induction of both allergen-specific (birch) and cross-reactive tolerance (hazelnut). In vivo, the beneficial effect of Bet-specific iTreg was verified in humanized mouse models of allergic airway and intestinal inflammation, resulting in reduced allergen-induced clinical symptoms and immune responses. Conclusion Human IL-10 DC-induced iTreg facilitate allergen-specific and cross-reactive tolerance. Therefore, they are potential candidates for regulatory cell therapy in allergic and autoimmune diseases.
17 Nov 2023Submitted to Allergy
17 Nov 2023Submission Checks Completed
17 Nov 2023Assigned to Editor
17 Nov 2023Review(s) Completed, Editorial Evaluation Pending
21 Nov 2023Reviewer(s) Assigned
10 Apr 20241st Revision Received
20 Jun 2024Submission Checks Completed
20 Jun 2024Assigned to Editor
20 Jun 2024Review(s) Completed, Editorial Evaluation Pending
26 Jun 2024Reviewer(s) Assigned
06 Jul 2024Editorial Decision: Accept