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.