title: STAT6 inhibitory peptide given during RSV infection of neonatal mice reduces exacerbated airway responses upon adult reinfection.
abstract: 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.
authors: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; and.
authors: Bharat T
authors: BT
authors: Srinivasa
authors: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; and.
authors: Katherine H
authors: KH
authors: Restori
authors: Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors: Jichuan
authors: J
authors: Shan
authors: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; and.
authors: Louis
authors: L
authors: Cyr
authors: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; and.
authors: Li
authors: L
authors: Xing
authors: Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors: Soojin
authors: S
authors: Lee
authors: Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada; and.
authors: Brian J
authors: BJ
authors: Ward
authors: Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada elizabeth.fixman@mcgill.ca.
authors: Elizabeth D
authors: ED
authors: Fixman
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism; D008168:Lung / Q000473:pathology* / Q000821:virology*; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology*; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000473:pathology / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000150:complications* / Q000473:pathology / Q000821:virology*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D050800:STAT6 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D000067596:Interleukin-33; D010455:Peptides; D050800:STAT6 Transcription Factor; D003094:Collagen; D000094632:Thymic Stromal Lymphopoietin
keywords: alternatively activated macrophages; asthma; collagen deposition; eosinophils; hyper-responsiveness