Taylor Samuel, Huang Yuefeng, Mallett Grace, Stathopoulou Chaido, Felizardo Tania C, Sun Ming-An, Martin Evelyn L, Zhu Nathaniel, Woodward Emma L, Elias Martina S, Scott Jonathan, Reynolds Nick J, Paul William E, Fowler Daniel H, Amarnath Shoba
Experimental Transplantation Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
J Exp Med. 2017 Jun 5;214(6):1663-1678. doi: 10.1084/jem.20161653. Epub 2017 May 10.
Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens and maintain tissue homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an important negative regulator of KLRG1 ILC-2 function in both mice and humans. Increase in KLRG1 ILC-2 cell numbers was attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During infection, a significant expansion of KLRG1 ILC-2 subsets occurred in mice and, upon adoptive transfer, KLRG1 ILC-2s significantly reduced worm burden. Furthermore, blocking PD-1 with an antibody increased KLRG1 ILC-2 cell number and reduced disease burden. Therefore, PD-1 is required for maintaining the number, and hence function, of KLRG1 ILC-2s.
第2组固有淋巴细胞（ILC-2s）调节对病原体的免疫反应，并响应细胞因子维持组织稳态。最近已阐明通过诱导共刺激分子（ICOS）对ILC-2s的正向调节作用。我们在此证明，程序性死亡受体1（PD-1）在小鼠和人类中都是杀伤细胞凝集素样受体G1（KLRG1）阳性ILC-2功能的重要负调节因子。KLRG1阳性ILC-2细胞数量的增加归因于PD-1信号传导的内在缺陷，这导致信号转导和转录激活因子5（STAT5）的激活增强。在感染期间，小鼠体内KLRG1阳性ILC-2亚群显著扩增，在过继转移后，KLRG1阳性ILC-2s显著减轻蠕虫负担。此外，用抗体阻断PD-1可增加KLRG1阳性ILC-2细胞数量并减轻疾病负担。因此，维持KLRG1阳性ILC-2s的数量及其功能需要PD-1。
