Prostaglandin I2 signaling and inhibition of Group 2 innate lymphoid cell responses

W. Zhou; S. Toki; J. Zhang; K. Goleniewksa; D.C. Newcomb; J.Y. Cephus; D.E. Dulek; M.H. Bloodworth; M.T. Stier; V. Polosuhkin; R.D. Gangula; S.A. Mallal; D.H. Broide; R.S. Peebles

doi:10.1164/rccm.201410-1793OC

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Prostaglandin I2 signaling and inhibition of Group 2 innate lymphoid cell responses

Journal article

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Prostaglandin I2 signaling and inhibition of Group 2 innate lymphoid cell responses

W. Zhou, S. Toki, J. Zhang, K. Goleniewksa, D.C. Newcomb, J.Y. Cephus, D.E. Dulek, M.H. Bloodworth, M.T. Stier, V. Polosuhkin, …

American Journal of Respiratory and Critical Care Medicine, Vol.193(1), pp.31-42

2016

DOI: https://doi.org/10.1164/rccm.201410-1793OC

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Abstract

RATIONALE: Group 2 innate lymphoid cells (ILC2s) robustly produce IL-5 and IL-13, cytokines central to the asthma phenotype; however, the effect of prostaglandin (PG) I2 on ILC2 function is unknown. OBJECTIVES: To determine the effect of PGI2 on mouse and human ILC2 cytokine expression in vitro and the effect of endogenous PGI2 and the PGI2 analog cicaprost on lung ILC2s in vivo. METHODS: Flow-sorted bone marrow ILC2s of wild-type (WT) and PGI2 receptor-deficient (IP(-/-)) mice were cultured with IL-33 and treated with the PGI2 analog cicaprost. WT and IP(-/-) mice were challenged intranasally with Alternaria alternata extract for 4 consecutive days to induce ILC2 responses, and these were quantified. Prior to A. alternata extract, challenged WT mice were treated with cicaprost. Human flow-sorted peripheral blood ILC2s were cultured with IL-33 and IL-2 and treated with the PGI2 analog cicaprost. MEASUREMENT AND MAIN RESULTS: We demonstrate that PGI2 inhibits IL-5 and IL-13 protein expression by IL-33-stimulated ILC2s purified from mouse bone marrow in a manner that was dependent on signaling through the PGI2 receptor IP. In a mouse model of 4 consecutive days of airway challenge with an extract of A. alternata, a fungal aeroallergen associated with severe asthma exacerbations, endogenous PGI2 signaling significantly inhibited lung IL-5 and IL-13 protein expression, and reduced the number of lung IL-5- and IL-13-expressing ILC2s, as well as the mean fluorescence intensity of IL-5 and IL-13 staining. In addition, exogenous administration of a PGI2 analog inhibited Alternaria extract-induced lung IL-5 and IL-13 protein expression, and reduced the number of lung IL-5- and IL-13-expressing ILC2s and the mean fluorescence intensity of IL-5 and IL-13 staining. Finally, a PGI2 analog inhibited IL-5 and IL-13 expression by human ILC2s that were stimulated with IL-2 and IL-33. CONCLUSIONS: These results suggest that PGI2 may be a potential therapy to reduce the ILC2 response to protease-containing aeroallergens, such as Alternaria.

Details

Title: Prostaglandin I2 signaling and inhibition of Group 2 innate lymphoid cell responses
Authors/Creators: W. Zhou (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
S. Toki (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
J. Zhang (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
K. Goleniewksa (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
D.C. Newcomb (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
J.Y. Cephus (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
D.E. Dulek (Author/Creator) - 2 Division of Infectious Diseases, Department of Pediatrics, and.
M.H. Bloodworth (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
M.T. Stier (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
V. Polosuhkin (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
R.D. Gangula (Author/Creator) - Vanderbilt University
S.A. Mallal (Author/Creator) - Vanderbilt University
D.H. Broide (Author/Creator) - University of California San Diego
R.S. Peebles (Author/Creator) - 1 Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine.
Publication Details: American Journal of Respiratory and Critical Care Medicine, Vol.193(1), pp.31-42
Publisher: American Thoracic Society
Identifiers: 991005544123907891
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.487 Regulatory T Cells
Web Of Science research areas: Critical Care Medicine; Respiratory System
ESI research areas: Clinical Medicine