Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90033, USA.
Oak Crest Institute of Science, Monrovia, CA 91016, USA.
Cells. 2020 Apr 15;9(4):974. doi: 10.3390/cells9040974.
Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have historically focused on morphological characterizations, but BG have also been implicated in viral antigen processing which suggests that they can serve a function in antiviral immunity. This study focused on investigating proteins that could be involved in BG formation to further characterize their structure using transmission electron microscopy (TEM). Here, we report a critical role for the protein annexin A2 (anxA2) in the proper formation of BG structures. When anxA2 expression is downregulated, langerin expression decreases, cytoplasmic BG are nearly ablated, and the presence of malformed BG-like structures increases. Furthermore, in the absence of anxA2, we found langerin was no longer localized to BG or BG-like structures. Taken together, these results indicate an essential role for anxA2 in facilitating the proper formation of BG.
郎格汉斯细胞（LC）是黏膜上皮的固有抗原提呈细胞，在启动免疫反应中发挥着重要作用。LC 是体内唯一含有 Birbeck 颗粒（BG）的细胞，BG 是由 c 型凝集素 langerin 组成的独特细胞质细胞器。对 BG 的研究历史上集中在形态特征上，但 BG 也与病毒抗原处理有关，这表明它们可以在抗病毒免疫中发挥作用。本研究重点研究了可能参与 BG 形成的蛋白质，使用透射电子显微镜（TEM）进一步表征其结构。在这里，我们报告了蛋白 annexin A2（anxA2）在 BG 结构的正确形成中的关键作用。当 anxA2 的表达下调时， langerin 的表达减少，细胞质 BG 几乎消失，并且出现了畸形的 BG 样结构增加。此外，在 anxA2 缺失的情况下，我们发现 langerin 不再定位于 BG 或 BG 样结构。综上所述，这些结果表明 anxA2 在促进 BG 的正确形成中起着至关重要的作用。
