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Prostaglandin I2 inhibits IL-33-induced IL-5 and IL-13 production by human type 2 innate lymphoid cells


Group 2 innate lymphoid cells (ILC2) are characterized by their expression of cytokines including IL-5 and IL-13 in response to IL-33. ILC2 are critical in mediating influenza virus-induced airway hypersensitivity and are associated with allergic inflammation. However, the factors regulating human ILC2 (hILC2) cytokine responses are not fully defined. In this study, we tested the hypothesis that prostaglandin I2 (PGI2), a lipid product formed in the cyclooxygenase (COX) pathway of arachidonic acid metabolism, suppresses IL-33-induced cytokine responses by hILC2.


hILC2 (Lin-CD25+CD127+ cells) were purified by flow cytometric cell sorting from peripheral blood mononuclear cells and stimulated with IL-33 and IL-2 in the presence of the PGI2 analog cicaprost or vehicle.


We found that hILC2 expressed the IL-33 receptor and the PGI2 receptor IP. Treatment of the cells with cicaprost significantly decreased IL-5 and IL-13 production, and the inhibition was associated with lower levels of mRNA expression of the transcription factors involved in the production of these cytokines and ILC2 development including gata3, gfi-1, Ror-α and Id2. cAMP-elevating reagents such as db-cAMP and PGE2 had a similar inhibitory effect on IL-5 and IL-13 production by hILC2.


These data indicate that PGI2 inhibits hILC2 cytokine secretion and suggest that use of COX inhibiting drugs may increase the risk of developing allergic diseases by augmenting ILC2 cytokine responses.

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Correspondence to Weisong Zhou.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Zhou, W., Goleniewska, K., Newcomb, D. et al. Prostaglandin I2 inhibits IL-33-induced IL-5 and IL-13 production by human type 2 innate lymphoid cells. World Allergy Organ J 8, A81 (2015).

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