@article {1051371,
	title = {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},
	journal = {J Allergy Clin Immunol},
	year = {2016},
	month = {2016 Oct 04},
	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.},
	issn = {1097-6825},
	doi = {10.1016/j.jaci.2016.08.034},
	author = {Rigas, Diamanda and Lewis, Gavin and Aron, Jennifer L and Wang, Bowen and Banie, Homayon and Sankaranarayanan, Ishwarya and Galle-Treger, Lauriane and Maazi, Hadi and Lo, Richard and Freeman, Gordon J and Sharpe, Arlene H and Soroosh, Pejman and Akbari, Omid}
}
