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Alarmins and innate lymphoid cells 2 activation: a common pathogenetic link connecting RSV bronchiolitis and later wheezing/asthma?
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  • Giovanni Rossi,
  • Stefania Ballarini,
  • Pietro Salvati,
  • Oliviero Sacco,
  • Andrew Colin
Giovanni Rossi
Ospedale Giannina Gaslini

Corresponding Author:giovannirossi@gaslini.org

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Stefania Ballarini
University of Perugia School of Medicine and Surgery
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Pietro Salvati
Ospedale Giannina Gaslini
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Oliviero Sacco
Istituto Giannina Gaslini
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Andrew Colin
University of Miami
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Abstract

Severe RSV infection in infancy is associated with increased risk of recurrent wheezing in childhood. Both acute and long-term alterations in airway functions are thought to be related to inefficient anti-viral immune response. The airway epithelium, the first target of respiratory syncytial virus (RSV), normally acts as an immunological barrier able to elicit an effective immune reaction but may also be programmed to directly promote a Th2 response, independently from Th2 lymphocyte involvement. Recognition of RSV transcripts and viral replication intermediates by bronchial epithelial cells brings about release of TSLP, IL-33, HMGB1 and IL-25, dubbed “alarmins”. These epithelial cell-derived proteins are particularly effective in stimulating innate lymphoid cells 2 (ILC2) to release IL-4, IL-5, and IL-13. ILC2, reflect the innate counterparts of Th2 cells and, when activate, are potent promoters of airway inflammation and hyperresponsiveness in RSV bronchiolitis and childhood wheezing/asthma. Long-term epithelial progenitors or persistent epigenetic modifications of the airway epithelium following RSV infection, may play a pathogenetic role in the short and long-term increased susceptibility to obstructive lung diseases in response to RSV in the young. Additionally, ILC2 function may be further regulated by RSV-induced changes in gut microbiota community composition that can be associated with disease severity in infants. A better understanding of the alarmin-ILC interactions in childhood might provide insights into the mechanisms characterizing these immune-mediated diseases and indicate new targets for prevention and therapeutic interventions.
02 Mar 2022Submitted to Pediatric Allergy and Immunology
08 Mar 2022Reviewer(s) Assigned
05 Apr 2022Review(s) Completed, Editorial Evaluation Pending
08 Apr 2022Editorial Decision: Revise Major
02 May 20221st Revision Received
03 May 2022Review(s) Completed, Editorial Evaluation Pending
04 May 2022Editorial Decision: Accept