Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
J Leukoc Biol. 2011 Jun;89(6):965-72. doi: 10.1189/jlb.1110611. Epub 2011 Mar 14.
NK cells have been increasingly reported to be an important effector in autoimmune diseases. However, nothing is known in this regard in DED, the most common eye pathology, which is characterized by sustained inflammation on the ocular surface. In the present study, we have examined the profile of NK cells on the ocular surface as well as in the draining lymphoid tissues during the development of this disease. Our data demonstrate activated NK cells during the disease-induction phase. Moreover, in vivo depletion of NK cells in mice results in reduced disease severity and diminished proinflammatory cytokines. Furthermore, we show that NK cells are also able to modulate the maturation of APCs, which is correlated with IFN-γ from NK cells. Together, our findings provide new in vivo evidence that IFN-γ-secreting NK cells can promote induction of DED via direct target tissue damage and indirect influence on the priming phase of an adaptive immune response in secondary lymphoid tissue.
自然杀伤 (NK) 细胞已被越来越多地报道为自身免疫性疾病中的一种重要效应细胞。然而，在以眼表面持续炎症为特征的最常见眼部病理学——干燥性角结膜炎 (DED) 中，这方面的信息尚未可知。在本研究中，我们研究了 NK 细胞在疾病发展过程中在眼表面以及引流淋巴组织中的特征。我们的数据表明 NK 细胞在疾病诱导阶段被激活。此外，在体内耗尽 NK 细胞可降低疾病严重程度并减少促炎细胞因子。此外，我们还表明 NK 细胞还能够调节 APC 的成熟，这与 NK 细胞产生的 IFN-γ 相关。总之，我们的研究结果提供了新的体内证据，表明 IFN-γ 分泌的 NK 细胞可通过直接靶向组织损伤和间接影响次级淋巴组织中适应性免疫反应的启动阶段来促进 DED 的诱导。
