Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Immunity. 2019 Oct 15;51(4):709-723.e6. doi: 10.1016/j.immuni.2019.09.005. Epub 2019 Oct 8.
Neuroimmune interactions have emerged as critical modulators of allergic inflammation, and type 2 innate lymphoid cells (ILC2s) are an important cell type for mediating these interactions. Here, we show that ILC2s expressed both the neuropeptide calcitonin gene-related peptide (CGRP) and its receptor. CGRP potently inhibited alarmin-driven type 2 cytokine production and proliferation by lung ILC2s both in vitro and in vivo. CGRP induced marked changes in ILC2 expression programs in vivo and in vitro, attenuating alarmin-driven proliferative and effector responses. A distinct subset of ILCs scored highly for a CGRP-specific gene signature after in vivo alarmin stimulation, suggesting CGRP regulated this response. Finally, we observed increased ILC2 proliferation and type 2 cytokine production as well as exaggerated responses to alarmins in mice lacking the CGRP receptor. Together, these data indicate that endogenous CGRP is a critical negative regulator of ILC2 responses in vivo.
神经免疫相互作用已成为过敏炎症的关键调节剂，2 型先天淋巴细胞 (ILC2) 是介导这些相互作用的重要细胞类型。在这里，我们表明 ILC2 表达神经肽降钙素基因相关肽 (CGRP) 及其受体。CGRP 在体外和体内均能强烈抑制警报素驱动的 2 型细胞因子产生和肺 ILC2 的增殖。CGRP 在体内和体外诱导 ILC2 表达程序的显著变化，减弱警报素驱动的增殖和效应器反应。在体内警报素刺激后，一个独特的 ILC 亚群对 CGRP 特异性基因特征评分很高，表明 CGRP 调节了这种反应。最后，我们观察到缺乏 CGRP 受体的小鼠中 ILC2 增殖和 2 型细胞因子产生增加以及对警报素的反应过度。总之，这些数据表明内源性 CGRP 是体内 ILC2 反应的关键负调节剂。
