Abstract:
:The seasonal burden of influenza coupled with the pandemic outbreaks of more pathogenic strains underscore a critical need to understand the pathophysiology of influenza injury in the lung. Interleukin-22 (IL-22) is a promising cytokine that is critical in protecting the lung during infection. This cytokine is strongly regulated by the soluble receptor IL-22-binding protein (IL-22BP), which is constitutively expressed in the lungs where it inhibits IL-22 activity. The IL-22/IL-22BP axis is thought to prevent chronic exposure of epithelial cells to IL-22. However, the importance of this axis is not understood during an infection such as influenza. Here we demonstrate through the use of IL-22BP-knockout mice (il-22ra2-/-) that a pro-IL-22 environment reduces pulmonary inflammation during H1N1 (PR8/34 H1N1) infection and protects the lung by promoting tight junction formation. We confirmed these results in normal human bronchial epithelial cells in vitro demonstrating improved membrane resistance and induction of the tight junction proteins Cldn4, Tjp1, and Tjp2. Importantly, we show that administering recombinant IL-22 in vivo reduces inflammation and fluid leak into the lung. Taken together, our results demonstrate the IL-22/IL-22BP axis is a potential targetable pathway for reducing influenza-induced pneumonia.
journal_name
Mucosal Immunoljournal_title
Mucosal immunologyauthors
Hebert KD,Mclaughlin N,Galeas-Pena M,Zhang Z,Eddens T,Govero A,Pilewski JM,Kolls JK,Pociask DAdoi
10.1038/s41385-019-0206-9subject
Has Abstractpub_date
2020-01-01 00:00:00pages
64-74issue
1eissn
1933-0219issn
1935-3456pii
10.1038/s41385-019-0206-9journal_volume
13pub_type
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