STAT6 inhibitory peptide given during RSV infection of neonatal mice reduces exacerbated airway responses upon adult reinfection

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

Ward, Brian J.¹  Shan, Jichuan¹  Xing, Li²  Cyr, Louis³  Lee, Soojin⁴  Restori, Katherine H.⁴  Fixman, Elizabeth D.⁴ 

[1] and;Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada;Meakins‐Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada

关键词: asthma;    eosinophils;    alternatively activated macrophages;    hyper‐;    responsiveness;    collagen deposition;   

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Respiratory syncytial virus (RSV)-related hospitalization during infancy is strongly associated with the subsequent development of asthma. Early life RSV infection results in a Th2-biased immune response, which is also typical of asthma. Murine models of neonatal RSV infection have been developed to examine the possible contribution of RSV-driven Th2 responses to the development of airway hyper-responsiveness later in childhood. We have investigated the ability of a cell-penetrating STAT6 inhibitory peptide (STAT6-IP), when delivered selectively during neonatal RSV infection, to modify pathogenesis induced upon secondary RSV reinfection of adults 6 wk later. Neonatal STAT6-IP treatment inhibited the development of airway hyper-responsiveness (AHR) and significantly reduced lung eosinophilia and collagen deposition in adult mice following RSV reinfection. STAT6-IP-treated, RSV-infected neonates had reduced levels of both IL-4 and alternatively activated macrophages (AAMs) in the lungs. Our findings suggest that targeting STAT6 activity at the time of early-life RSV infection may effectively reduce the risk of subsequent asthma development.

【 授权许可】

CC BY