CD8 T cell response and its released cytokine IFN-γ are necessary for lung alveolar epithelial repair during bacterial pneumonia.
CD8 T cell response and its released cytokine IFN-γ are necessary for lung alveolar epithelial repair during bacterial pneumonia.
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CD 8 T细胞反应及其释放的细胞因子IFN-γ是细菌性肺炎肺泡上皮细胞修复所必需的。
DOI：
10.3389/fimmu.2023.1268078
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发表时间：
2023
影响因子：
7.3
通讯作者：
Tian, Ying
中科院分区：
文献类型：
--
作者：
Zhang, Xiaoying;Ali, Mir;Pantuck, Morgan Alexandra;Yang, Xiaofeng;Lin, Chih-Ru;Bahmed, Karim;Kosmider, Beata;Tian, Ying
肺泡上皮细胞的再生依赖于静止祖细胞的活性。肺泡上皮II型（AT 2）细胞被称为肺泡上皮祖细胞。它们退出静止状态，响应损伤而快速增殖，并分化为肺泡上皮I型（AT 1）细胞以再生受损的肺泡上皮。虽然AT 2细胞可塑性一直是一个非常激烈的研究领域，但CD 8 T细胞应答及其释放的细胞因子IFN-γ在调节AT 2细胞可塑性和损伤后肺泡上皮修复和再生中的作用仍然很大程度上未知。我们使用流式细胞术定量小鼠肺炎链球菌引起的细菌性肺炎后肺中CD 8 T细胞的数量。为了确定在肺泡上皮再生期间，CD 8 T细胞及其释放的细胞因子IFN-γ是否是AT 2细胞活性所必需的，我们使用抗CD 8或抗IFN-γ单克隆抗体（mAb）治疗进行了体内功能丧失研究。我们采用AT 2-CD 8 T细胞共培养系统，在体外评估了CD 8 T细胞和细胞因子IFN-γ对AT 2细胞分化能力的影响。我们检测到小鼠肺中CD 8 T细胞的瞬时积累波，这与肺炎链球菌引起的细菌性肺炎小鼠肺泡上皮修复和再生过程中AT 2细胞增殖的爆发相一致。用抗CD 8或抗IFN-γ单克隆抗体耗竭CD 8 T细胞或中和细胞因子IFN-γ可显著降低细菌性肺炎后小鼠AT 2细胞增殖和向AT 1细胞分化。此外，CD 8 T细胞或细胞因子IFN-γ与AT 2细胞的共培养促进了鼠和人系统中的AT 2-至-AT 1细胞分化。相反，阻断IFN-γ信号传导消除了AT 2-CD 8 T细胞共培养系统中AT 2-至-AT 1细胞分化的增加。我们的数据表明，CD 8 T细胞反应和细胞因子IFN-γ是必要的，以促进AT 2细胞活性在肺泡上皮修复和再生后，由细菌性肺炎引起的急性肺损伤。
Alveolar epithelial regeneration depends on the activity of resident quiescent progenitor cells. Alveolar epithelial type II (AT2) cells are known as the alveolar epithelial progenitor cells. They exit quiescent state, proliferate rapidly in response to injury and differentiate into alveolar epithelial type I (AT1) cells to regenerate the damaged alveolar epithelium. Although AT2 cell plasticity has been a very intense field of research, the role of CD8 T cell response and their released cytokine IFN-γ, in regulating AT2 cell plasticity and alveolar epithelial repair and regeneration after injury remains largely unknown. We used flow cytometry to quantify the amount of CD8 T cells in mouse lungs after bacterial pneumonia caused by Streptococcus pneumoniae. To determine whether CD8 T cells and their released cytokine IFN-γ are necessary for AT2 cell activity during alveolar epithelial regeneration, we performed loss of function studies using anti-CD8 or anti-IFN-γ monoclonal antibody (mAb) treatment in vivo. We assessed the effects of CD8 T cells and cytokine IFN-γ on AT2 cell differentiation capacity using the AT2- CD8 T cell co-culture system in vitro. We detected a transient wave of accumulation of CD8 T cells in mouse lungs, which coincided with the burst of AT2 cell proliferation during alveolar epithelial repair and regeneration in mice following bacterial pneumonia caused by Streptococcus pneumoniae. Depletion of CD8 T cells or neutralization of cytokine IFN-γ using anti-CD8 or anti-IFN-γ monoclonal antibody significantly reduced AT2 cell proliferation and differentiation into AT1 cells in mice after bacterial pneumonia. Furthermore, co-culture of CD8 T cells or cytokine IFN-γ with AT2 cells promoted AT2-to-AT1 cell differentiation in both murine and human systems. Conversely, blockade of IFN-γ signaling abrogated the increase in AT2-to-AT1 cell differentiation in the AT2- CD8 T cell co-culture system. Our data demonstrate that CD8 T-cell response and cytokine IFN-γ are necessary for promoting AT2 cell activity during alveolar epithelial repair and regeneration after acute lung injury caused by bacterial pneumonia.
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影响因子：
23.9
作者：
Lechner AJ;Driver IH;Lee J;Conroy CM;Nagle A;Locksley RM;Rock JR
通讯作者：
Rock JR
影响因子：
1.2
作者：
Chamoto, Kenji;Gibney, Barry C.;Lee, Grace S.;Ackermann, Maximilian;Konerding, Moritz A.;Tsuda, Akira;Mentzer, Steven J.
通讯作者：
Mentzer, Steven J.
DOI：
10.1165/rcmb.2012-0030oc
发表时间：
2012-10-01
影响因子：
6.4
作者：
Chen, Leiling;Acciani, Thomas;Perl, Anne-Karina T.
通讯作者：
Perl, Anne-Karina T.
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.7
作者：
Kosmider B;Messier EM;Chu HW;Mason RJ
通讯作者：
Mason RJ