College of Life Science and Bio-engineering, Beijing Molecular Hydrogen Research Center, Beijing University of Technology, Beijing, 100124, People's Republic of China.
Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People's Republic of China.
Cell Commun Signal. 2018 Oct 22;16(1):70. doi: 10.1186/s12964-018-0284-4.
Benign Lymphoepithelial Lesion (BLEL) is a rare disease observed in the adult population. Despite the growing numbers of people suffering from BLEL, the etiology and mechanisms underlying its pathogenesis remain unknown.
In the present study, we used gene and cytokines expression profiling, western blot and immunohistochemistry to get further insight into the cellular and molecular mechanisms involved in the pathogenesis of BLEL of the lacrimal gland.
The results showed that Macrophage Migration Inhibitory Factor (MIF) was the most highly expressed cytokine in BLEL, and its expression positively correlated with the expression of Th2 and Th17 cells cytokines. MIF was found to regulate biological functions and pathways involved in BLEL pathogenesis, such as proliferation, resistance to apoptosis, MAPK and PI3K/Akt pathways. We also found that MIF promotes fibrosis in BLEL by inducing BLEL fibroblast differentiation into myofibroblasts as well as the synthesis and the deposit of extracellular matrix in BLEL tissues.
Our findings demonstrate the contribution of MIF to the pathogenesis of BLEL of the lacrimal gland and suggested MIF as a promising therapeutic target for its treatment.
良性淋巴上皮病变（BLEL）是一种在成年人群中观察到的罕见疾病。尽管越来越多的人患有 BLEL，但它的发病机制的病因和机制仍不清楚。
在本研究中，我们使用基因和细胞因子表达谱、western blot 和免疫组织化学来进一步深入了解与泪腺 BLEL 发病机制相关的细胞和分子机制。
结果表明，巨噬细胞移动抑制因子（MIF）是 BLEL 中表达最高的细胞因子，其表达与 Th2 和 Th17 细胞细胞因子的表达呈正相关。发现 MIF 调节与 BLEL 发病机制相关的生物学功能和途径，如增殖、抗凋亡、MAPK 和 PI3K/Akt 途径。我们还发现，MIF 通过诱导 BLEL 成纤维细胞分化为肌成纤维细胞以及 BLEL 组织中细胞外基质的合成和沉积，促进 BLEL 中的纤维化。
我们的研究结果表明 MIF 参与了泪腺 BLEL 的发病机制，并提示 MIF 是其治疗的一个有前途的治疗靶点。
