• Ben Roediger, Ryan Kyle, Szun S Tay, Andrew J Mitchell, Holly A Bolton, Thomas V Guy, Sioh-Yang Tan, Elizabeth Forbes-Blom, Philip L Tong, Yasmin Köller, Elena Shklovskaya, Makio Iwashima, Kathy D McCoy, Graham Le Gros, Barbara Fazekas de St Groth, and Wolfgang Weninger.
• Centenary Institute, Newtown, Australia; Discipline of Dermatology, Sydney Medical School, University of Sydney, Sydney, Australia. Electronic address: b.roediger@centenary.org.au.
• J. Allergy Clin. Immunol. 2015 Dec 1; 136 (6): 1653-1663.e7.

BackgroundGroup 2 innate lymphoid cells (ILC2) have been implicated in the pathogenesis of allergic lung diseases. However, the upstream signals that regulate ILC2 function during pulmonary inflammation remain poorly understood. ILC2s have been shown to respond to exogenous IL-2, but the importance of endogenous IL-2 in ILC2 function in vivo remains unclear.ObjectiveWe sought to understand the role of IL-2 in the regulation of ILC2 function in the lung.MethodsWe used histology, flow cytometry, immunohistochemistry, ELISA, and quantitative PCR with knockout and reporter mice to dissect pulmonary ILC2 function in vivo. We examined the role of ILC2s in eosinophilic crystalline pneumonia, an idiopathic type 2 inflammatory lung condition of mice, and the effect of IL-2 deficiency on this disease. We determined the effect of IL-2 administration on pulmonary ILC2 numbers and function in mice in the steady state and after challenge with IL-33.ResultsWe discovered an unexpected role for innate cell-derived IL-2 as a major cofactor of ILC2 function during pulmonary inflammation. Specifically, we found that IL-2 was essential for the development of eosinophilic crystalline pneumonia, a type 2 disease characterized by increased numbers of activated ILC2s. We show that IL-2 signaling serves 2 distinct functions in lung ILC2s, namely promoting cell survival/proliferation and serving as a cofactor for the production of type 2 cytokines. We further demonstrate that group 3 innate lymphoid cells are an innate immune source of IL-2 in the lung.ConclusionInnate cell-derived IL-2 is a critical cofactor in regulating ILC2 function in pulmonary type 2 pathology.Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

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