IL-33 Receptor (ST2) Signalling is Important for Regulation of Th2-Mediated Airway Inflammation in a Murine Model of Acute Respiratory Syncytial Virus Infection

Abstract

T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is the ligand-binding component of the receptor for the cytokine IL-33, a newly identified cytokine known to amplify the Th2 cell-dominant immune responses. The function of IL-33/ST2 signalling during respiratory syncytial virus (RSV) infection is not fully known. In this study, following intranasal infection with RSV, BALB/c mice showed a marked increase in the production of IL-33, with an elevated expression of ST2 mRNA as well as a massive infiltration of CD45+ST2+ cells in the lungs, suggesting that during the early phase of RSV infection, IL-33 target cells which express ST2 on cell surface, may play a critical role for the development of RSV-induced airway inflammation. Indeed, blocking ST2 signalling using anti-ST2 monoclonal antibody diminished not only RSV-induced eosinophil recruitment, but also the amounts of Th2-associated cytokines, particularly IL-13, and Th17-type cytokine IL-17A in the lungs of infected mice. However, anti-ST2 antibody treatment did not affect the production of Th1-type cytokine IFN-γ as well as pulmonary viral growth and clearance. These results indicate that IL-33/ST2 signalling is involved in RSV-induced, Th2-associated airway inflammation but not protective immunity.