IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection.
IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection.
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作者：
流感感染主要针对上呼吸道系统，导致上皮细胞层严重破坏。免疫细胞在气管和支气管上皮细胞再生中的作用尚不明确。在这里，我们研究了流感感染期间支气管肺泡灌洗液（BAL）、气管、肺组织和脾脏中促生长细胞因子白介素-22 （IL-22）的产生。我们发现，在BAL、气管和肺组织中，常规NK细胞（NCR1+NK1.1+CD127−RORγt−）是主要的il -22产生细胞。在野生型（WT）小鼠中，气管上皮细胞组成性地表达高水平的IL-22R，并在IL-22的作用下活跃增殖。IL-22 - / -小鼠感染流感病毒后，气管上皮细胞再生受到严重损害。此外，即使在感染后10天（DPI 10）， IL-22−/−小鼠的体重继续下降，没有任何恢复。IL-22−/−小鼠在流感感染期间气管上皮细胞增殖显著降低。将IL-22充足但不缺乏的NK细胞过继转移到IL-22 - / -小鼠中，可恢复气管/支气管上皮细胞的再生，并具有抗炎症的保护作用。我们的研究结果强烈表明，传统NK细胞已经进化到既可以杀死病毒感染的细胞，又可以为组织再生提供重要的细胞因子。
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 NK cells (NCR1+NK1.1+CD127−RORγt−) 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 (WT) 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 (DPI 10) 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.
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影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
DOI：
10.1590/s1807-59322010001200003
发表时间：
2010
期刊：
Clinics (Sao Paulo, Brazil)
影响因子：
--
作者：
Capelozzi VL;Parra ER;Ximenes M;Bammann RH;Barbas CS;Duarte MI
通讯作者：
Duarte MI
影响因子：
4.4
作者：
Dhiman, Rohan;Indramohan, Mohanalaxmi;Vankayalapati, Ramakrishna
通讯作者：
Vankayalapati, Ramakrishna
白介素（IL）-15R [alpha] - 缺陷的天然杀伤细胞在正常但IL-15R [alpha]缺陷小鼠中生存。
影响因子：
15.3
作者：
Koka, R;Burkett, PR;Chien, M;Chai, S;Chan, F;Lodolce, JP;Boone, DL;Ma, A
通讯作者：
Ma, A
影响因子：
6.4
作者：
Kash JC;Walters KA;Davis AS;Sandouk A;Schwartzman LM;Jagger BW;Chertow DS;Li Q;Kuestner RE;Ozinsky A;Taubenberger JK
通讯作者：
Taubenberger JK