1. Type 2 innate lymphoid cell suppression by regulatory T cells attenuates airway hyperreactivity and requires inducible T-cell costimulator-inducible T-cell costimulator ligand interaction.
- Author
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Rigas D, Lewis G, Aron JL, Wang B, Banie H, Sankaranarayanan I, Galle-Treger L, Maazi H, Lo R, Freeman GJ, Sharpe AH, Soroosh P, and Akbari O
- Subjects
- Animals, Bronchoalveolar Lavage Fluid immunology, Cells, Cultured, Coculture Techniques, Disease Models, Animal, Humans, Immunity, Innate, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Asthma immunology, Cytokines immunology, Lymphocytes immunology
- Abstract
Background: Atopic diseases, including asthma, exacerbate type 2 immune responses and involve a number of immune cell types, including regulatory T (Treg) cells and the emerging type 2 innate lymphoid cells (ILC2s). Although ILC2s are potent producers of type 2 cytokines, the regulation of ILC2 activation and function is not well understood., Objective: In the present study, for the first time, we evaluate how Treg cells interact with pulmonary ILC2s and control their function., Methods: ILC2s and Treg cells were evaluated by using in vitro suppression assays, cell-contact assays, and gene expression panels. Also, human ILC2s and Treg cells were adoptively transferred into NOD SCID γC-deficient mice, which were given isotype or anti-inducible T-cell costimulator ligand (ICOSL) antibodies and then challenged with IL-33 and assessed for airway hyperreactivity., Results: We show that induced Treg cells, but not natural Treg cells, effectively suppress the production of the ILC2-driven proinflammatory cytokines IL-5 and IL-13 both in vitro and in vivo. Mechanistically, our data reveal the necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 suppression alongside the suppressive cytokines TGF-β and IL-10. Using a translational approach, we then demonstrate that human induced Treg cells suppress syngeneic human ILC2s through ICOSL to control airway inflammation in a humanized ILC2 mouse model., Conclusion: These findings suggest that peripheral expansion of induced Treg cells can serve as a promising therapeutic target against ILC2-dependent asthma., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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