Medical College of Wisconsin
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IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection. Mucosal Immunol 2013 Jan;6(1):69-82

Date

06/29/2012

Pubmed ID

22739232

Pubmed Central ID

PMC3835350

DOI

10.1038/mi.2012.49

Scopus ID

2-s2.0-84867658823 (requires institutional sign-in at Scopus site)   164 Citations

Abstract

Influenza infection primarily targets the upper respiratory system, leading to a severe destruction of the epithelial cell layer. The role of immune cells in the regeneration of tracheal and bronchial epithelial cells is not well defined. Here, we investigated the production of pro-constructive cytokine, Interleukin-22 (IL-22), in the bronchoalveolar lavage (BAL), trachea, lung tissue, and spleen during influenza infection. We found that conventional natural killer (NK) cells (NCR1(+)NK1.1(+)CD127(-)RORĪ³t(-)) were the predominant IL-22-producers in the BAL, trachea, and lung tissues. Tracheal epithelial cells constitutively expressed high levels of IL-22R and underwent active proliferation in response to IL-22 in the wild-type mice. Infection of IL-22(-/-) mice with influenza virus resulted in a severe impairment in the regeneration of tracheal epithelial cells. In addition, IL-22(-/-) mice continued to lose body weight even after 10 days post infection without any recovery. Tracheal epithelial cell proliferation was significantly reduced in IL-22(-/-) mice during influenza infection. Adoptive transfer of IL-22-sufficient but not IL-22-deficient NK cells into IL-22(-/-) mice restored the tracheal/bronchial epithelial cell regeneration and conferred protection against inflammation. Our findings strongly suggest that conventional NK cells have evolved to both kill virus-infected cells and also to provide vital cytokines for tissue regeneration.

Author List

Kumar P, Thakar MS, Ouyang W, Malarkannan S

Author

Subramaniam Malarkannan PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adoptive Transfer
Animals
Bronchoalveolar Lavage Fluid
Cell Proliferation
Epithelial Cells
Humans
Inflammation
Interleukins
Killer Cells, Natural
Lung
Mice
Natural Cytotoxicity Triggering Receptor 1
Orthomyxoviridae
Orthomyxoviridae Infections
Regeneration
Respiratory Mucosa
Spleen
Trachea