Arpaia Nicholas, Green Jesse A, Moltedo Bruno, Arvey Aaron, Hemmers Saskia, Yuan Shaopeng, Treuting Piper M, Rudensky Alexander Y
Howard Hughes Medical Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Howard Hughes Medical Institute and Ludwig Center at Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; The David Rockefeller Graduate Program, The Rockefeller University, New York, NY 10065, USA.
Cell. 2015 Aug 27;162(5):1078-89. doi: 10.1016/j.cell.2015.08.021.
Regulatory T (Treg) cells suppress immune responses to a broad range of non-microbial and microbial antigens and indirectly limit immune inflammation-inflicted tissue damage by employing multiple mechanisms of suppression. Here, we demonstrate that selective Treg cell deficiency in amphiregulin leads to severe acute lung damage and decreased blood oxygen concentration during influenza virus infection without any measureable alterations in Treg cell suppressor function, antiviral immune responses, or viral load. This tissue repair modality is mobilized in Treg cells in response to inflammatory mediator IL-18 or alarmin IL-33, but not by TCR signaling that is required for suppressor function. These results suggest that, during infectious lung injury, Treg cells have a major direct and non-redundant role in tissue repair and maintenance-distinct from their role in suppression of immune responses and inflammation-and that these two essential Treg cell functions are invoked by separable cues.
调节性T（Treg）细胞通过多种抑制机制抑制对广泛的非微生物和微生物抗原的免疫反应，并间接限制免疫炎症造成的组织损伤。在此，我们证明，在双调蛋白中选择性Treg细胞缺陷会导致流感病毒感染期间严重的急性肺损伤和血氧浓度降低，而Treg细胞抑制功能、抗病毒免疫反应或病毒载量没有任何可测量的改变。这种组织修复方式是Treg细胞响应炎症介质白细胞介素-18或警报素白细胞介素-33而动员起来的，但不是由抑制功能所需的TCR信号传导所动员。这些结果表明，在感染性肺损伤期间，Treg细胞在组织修复和维持中具有主要的直接和非冗余作用——这与其在抑制免疫反应和炎症中的作用不同——并且这两种基本的Treg细胞功能是由可分离的信号激活的。
