Targeting the IL-22/IL-22BP axis enhances tight junctions and reduces inflammation during influenza infection.

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 Immunol

journal_title

Mucosal immunology

authors

Hebert KD,Mclaughlin N,Galeas-Pena M,Zhang Z,Eddens T,Govero A,Pilewski JM,Kolls JK,Pociask DA

doi

10.1038/s41385-019-0206-9

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

64-74

issue

1

eissn

1933-0219

issn

1935-3456

pii

10.1038/s41385-019-0206-9

journal_volume

13

pub_type

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