Toll-like Receptors Regulate MIF Expression in Benign Lymphoepithelial Lesion of the Lacrimal Gland

Despite a perpetual increase in the prevalence of benign lymphoepithelial lesion, data on the mechanisms governing its pathogenesis are still missing. Thus, we aimed in the present study to evaluate whether TLRs could regulate the expression of the pleiotropic pro-inflammatory and tumor-related cytokine MIF in BLEL. Using gene expression profiling and protein expression analysis methods, we found that TLRs were overexpressed and that their signaling pathways were activated in BLEL. We have also confirmed in tissues biopsies, the overexpression of MIF reported previously in plasma of BLEL specimen. The analysis of the TLR7/8 impact on the expression of MIF in BLEL primary cells showed that when activated, TLR7/8 stimulate mainly BLEL lymphocytes to release MIF but not the fibroblast-like cells. No significant change was observed when MIF expression was investigated at the transcriptional level 24h post TLR7/8 activation. Taken together, these data suggest that TLR7 and TLR8 are activated in BLEL and may induce a cell type-dependent regulation of MIF secretion and expression

Macrophage migration inhibitory factor contributes to the pathogenesis of benign lymphoepithelial lesion of the lacrimal gland

Abstract Background 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. Methods 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. Results 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. Conclusions 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