Adenosine receptors differentially regulate type 2 cytokine production by IL‐33–activated bone marrow cells, ILC2s, and macrophages

Group 2 innate lymphoid cells (ILC2s) represent a rapid source of type 2 cytokines, such as IL‐5 and IL‐13, and play an important role in orchestrating type 2 immune response. Adenosine is an endogenous purine nucleoside, a catabolite of ATP that binds and activates ≥1 of 4 transmembrane G protein–coupled cell‐surface adenosine receptors (ARs)—A 1 , A 2A , A 2B , and A 3 . Here, we studied the role of ARs in the regulation of cytokine production by ILC2s. We found that A 2B ARs suppress the production of both IL‐5 and IL‐13 by ILC2s, whereas A 2A ARs augment IL‐5 production and fail to affect IL‐13 release. Combined stimulation of all ARs led to the suppression of both IL‐5 and IL‐13 production, which indicated that A 2B ARs dominate A 2A ARs. Both pre‐ and post‐transcriptional processes may be involved in the AR modulation of ILC2 IL‐5 and IL‐13 production. Thus, we identify adenosine as a novel negative regulator of ILC2 activation.—Csóka, B., Németh, Z. H., Duerr, C. U., Fritz, J. H., Pacher, P., Haskó, G. Adenosine receptors differentially regulate type 2 cytokine production by IL‐33–activated bone marrow cells, ILC2s, and macrophages. FASEB J. 32, 829–837 (2018). www.fasebj.org