Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.
Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Beijing, China.
Am J Transplant. 2019 Mar;19(3):662-673. doi: 10.1111/ajt.15084. Epub 2018 Sep 24.
Beyond their historical role as the effector cells in allergic disorders, mast cells have been implicated in regulating both innate and adaptive immune responses. Possessing considerable functional plasticity, mast cells are abundant at mucosal surfaces, where the host and external environments interface. The purpose of this study was to evaluate the contribution of mast cells to allograft rejection at the ocular surface. Using a well-characterized murine model of corneal transplantation, we report that mast cells promote allosensitization. Our data show mast cell frequencies and activation are increased following transplantation. We demonstrate that mast cell inhibition (a) limits the infiltration of inflammatory cells and APC maturation at the graft site; (b) reduces allosensitization and the generation of Th1 cells in draining lymphoid tissues; (c) decreases graft infiltration of alloimmune-inflammatory cells; and (d) prolongs allograft survival. Our data demonstrate a novel function of mast cells in promoting allosensitization at the ocular surface.
除了在过敏疾病中作为效应细胞的历史作用外，肥大细胞还被认为参与调节先天和适应性免疫反应。肥大细胞具有相当大的功能可塑性，在宿主和外部环境相互作用的黏膜表面丰富存在。本研究旨在评估肥大细胞在眼表面同种异体移植物排斥中的作用。我们使用一种经过充分表征的角膜移植鼠模型，报告称肥大细胞促进同种致敏。我们的数据表明，移植后肥大细胞的频率和激活增加。我们证明肥大细胞抑制（a）限制移植物部位炎症细胞和 APC 成熟的浸润；（b）减少引流淋巴组织中的同种致敏和 Th1 细胞的产生；（c）减少同种免疫炎症细胞对移植物的浸润；（d）延长同种异体移植物的存活期。我们的数据表明肥大细胞在促进眼表面同种致敏方面具有新的功能。
