Targeting the P2Y13 Receptor Suppresses IL-33 and HMGB1 Release and Ameliorates Experimental Asthma

• Published in: American journal of respiratory and critical care medicine Vol. 205; no. 3; pp. 300 - 312
• Main Authors: Werder, Rhiannon B, Ullah, Ashik, Rahman, Muhammed Mahfuzur, Simpson, Jennifer, Lynch, Jason P, Collinson, Natasha, Rittchen, Sonja, Rashid, Ridwan B, Sikder, Al Amin, Handoko, Herlina Y, Curren, Bodie F, Sebina, Ismail, Hartel, Gunter, Bissell, Alec, Ngo, Sylvia, Yarlagadda, Tejasri, Hasnain, Sumaira Z, Lu, Wenying, Sohal, Sukhwinder S, Martin, Megan, Bowler, Simon, Burr, Lucy D, Martinez, Laurent O, Robaye, Bernard, Spann, Kirsten, Ferreira, Manuel A R, Phipps, Simon
• Format: Journal Article
• Language: English
• Published: New York American Thoracic Society 01.02.2022
• Subjects: Antagonist drugs; Asthma; Cytokines; Original; Pharmacology; Proteins
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.202009-3686OC

Werder et al discuss their study which aims to determine whether P2Y13-R (P2Y13 receptor), a purinergic GPCR (G protein-coupled receptor) and risk allele for asthma, regulates the release of IL-33 and HMGB1 (high mobility group box 1). The role of P2Y13-R in AEC function and in the onset, progression, and exacerbation of experimental asthma was assessed by using pharmacological antagonists and mice with P2Y13-R gene deletion. They identify P2Y13-R as a novel gatekeeper of the nuclear alarmins IL-33 and HMGB1 and demonstrate that the targeting of this GPCR via genetic deletion or treatment with a small-molecule antagonist protects against the onset and exacerbations of experimental asthma.