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Fevipiprant, a selective prostaglandin D2 receptor 2 antagonist, inhibits human group 2 innate lymphoid cell aggregation and function Clare Hardman, PhD, Wentao Chen, MSc, Jian Luo, MD, Paul Batty, MSc, Yi-Ling Chen, DPhil, Janina Nahler, BSc, Yanqiu Wu, MM, Ian D. Pavord, F Med Sci, Veit J. Erpenbeck, MD, David A. Sandham, PhD, Luzheng Xue, PhD, Graham Ogg, BMBCh DPhil Journal of Allergy and Clinical Immunology Volume 143, Issue 6, Pages (June 2019) DOI: /j.jaci Copyright © 2019 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 1 Effect of fevipiprant on ILC2 migration, survival, and cytokine production. A-C, ILC2 migration to PGD2 (200 nmol/L) in the presence of 1 μmol/L fevipiprant (Fig 1, A) or concentration range of fevipiprant (Fig 1, B) determined with IncuCyte and ILC2 survival measured by using flow cytometry (Fig 1, C). D-G, ILC2s were incubated with combinations of PGD2 (200 nmol/L) and fevipiprant (0.01 nmol/L to 1 μmol/L), and measurements were taken of type 2 cytokine gene expression (Fig 1, D) and protein production (Fig 1, E) and GM-CSF, colony-stimulating factor 1 (CSF-1), and IL-8 gene expression (Fig 1, F) and protein production (Fig 1, G). H, Asthmatic donor (mild-to-moderate asthma, n = 3; severe asthma, n = 3 donors) ILC2s were incubated with combinations of PGD2 (200 nmol/L) and fevipiprant (0.01 nmol/L to 1 μmol/L), and cytokine production was measured. Data are representative of at least 3 independent experiments per donor (n = 3-6 donors). Values are presented as means ± SEMs. Journal of Allergy and Clinical Immunology , DOI: ( /j.jaci ) Copyright © 2019 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 2 Effect of fevipiprant on ILC2 aggregation and cytokine production. A-C, ILC2 aggregation induced by PGD2 (200 nmol/L) in the presence of fevipiprant (0.01 nmol/L to 1 μmol/L) measured by means of microscopy in healthy donors (Fig 2, A and B) and asthmatic donors (Fig 2, C). D and E, Adhesion molecule gene expression: ICAM1 (Fig 2, D) and PECAM1 (Fig 2, E) were measured by using quantitative PCR. F, ICAM-1 and PECAM-1 blockade effect on PGD2-induced ILC2 aggregation. G, Effect of fevipiprant (1 μmol/L) and anti–ICAM-1 (20 μg/mL) and anti–PECAM-1 (40 μg/mL) on ILC2 cytokine production after PGD2 stimulation. Data are representative of at least 3 independent experiments (n = 3-6 donors). Values are presented as means ± SEMs. Journal of Allergy and Clinical Immunology , DOI: ( /j.jaci ) Copyright © 2019 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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