IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection

被引:145
作者
Kumar, P. [1 ]
Thakar, M. S. [2 ]
Ouyang, W. [3 ]
Malarkannan, S. [1 ,4 ,5 ]
机构
[1] Blood Res Inst, Lab Mol Immunol & Immunotherapy, Milwaukee, WI USA
[2] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA
[3] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA
[4] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA
[5] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA
关键词
RECEPTOR-ALPHA-CHAIN; NATURAL-KILLER-CELLS; ROR-GAMMA-T; FUNCTIONAL EXPRESSION; POTENTIAL ROLE; DIFFERENTIATION; INTERLEUKIN-22; IL-15; INNATE; RECOGNITION;
D O I
10.1038/mi.2012.49
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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(-)ROR gamma t(-)) 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.
引用
收藏
页码:69 / 82
页数:14
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