The FcεRI signaling pathway is involved in the pathogenesis of lacrimal gland benign lymphoepithelial lesions as shown by transcriptomic analysis

This study aimed to analyze the role of the FcepsilonRI (FcεRI) signaling pathway in the pathogenesis of benign lymphoepithelial lesion of lacrimal gland (LGBLEL). Transcriptomic analysis was performed on LGBLEL and orbital cavernous hemangioma (CH) patients diagnosed via histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013. Four LGBLEL and three orbital CH patients, diagnosed between October 2018 and August 2019, were randomly selected as experimental and control groups, respectively. RT-PCR, immunohistochemical staining, and western blotting were used to verify genes and proteins related to the FcεRI signaling pathway. Transcriptomic analysis showed that the FcεRI signaling pathway was upregulated in the LGBLEL compared with the CH group. The mRNA expression levels of important genes including SYK, p38, JNK, PI3K, and ERK were significantly increased in the LGBLEL group (P = 0.0066, P = 0.0002, P = 0.0003, P < 0.0001, P < 0.0001, respectively). Immunohistochemical staining results showed that SYK, p38, and ERK were positively expressed in LGBLEL, while JNK and PI3K were not. The protein contents of P-SYK, P-p38, P-JNK, P-PI3K, and P-ERK were significantly higher in the LGBLEL than in the CH group (P = 0.0169, P = 0.0074, P = 0.0046, P = 0.0157, P = 0.0156, respectively). The FcεRI signaling pathway participates in the pathogenesis of LGBLEL.

Differences in Immune Indicators and Prognosis Between IgG4-Positive and Negative Lacrimal Gland Benign Lymphoepithelial Lesion

Purpose: The differences in immune indicators and prognosis between IgG4-positive and negative lacrimal gland benign lymphoepithelial lesion (LGBLEL) were analyzed.Methods: This was a single-center retrospective clinical study. Clinical data of 146 patients with LGBLEL were collected from June 2011 to June 2019. Results: The age, preoperative glucocorticoid history, and serum C3, C4, IgG, IgG2, IgG4 had statistical difference between the IgG4-positive and negative groups (P<0.05). The expression levels of IgG and IgG4 in the IgG-positive group with preoperative glucocorticoid therapy were lower than those in the IgG4-negative group without preoperative glucocorticoid therapy (P=0.021 and P=0.013). The 5-year recurrence-free cumulative percentages of IgG4-positive group was 81.85%, and 83.46% in the IgG-negative group, which had no statistical difference (P=0.216). The history of preoperative glucocorticoid therapy, serum C4, IgG1 and IgG2 were the factors affecting IgG4-positive LGBLEL’ recurrence, while the history of preoperative glucocorticoid therapy, serum C4, and IgG1 were the factors affecting LGBLEL’ recurrence (P<0.05).Conclusion: Serum C3, C4, IgG, IgG2, IgG4 had statistical difference between the IgG4-positive and negative LGBLEL. The history of preoperative glucocorticoid therapy, serum C4 and IgG1 were the factors affecting LGBLEL’ recurrence, while the expression level of IgG4 was not the factor affecting LGBLEL’ recurrence.

The Involvement of the Fcεri Signaling Pathway in the Pathogenesis of Lacrimal Gland Benign Lymphoepithelial Lesions

Objective: Benign lymphoepithelial lesion of lacrimal gland (LGBLEL) is a common orbital inflammatory disease with unknown pathogenesis. T his paper analyzed the role of the FcepsilonRI (FcεRI) signaling pathway in the pathogenesis of LGBLEL.Methods: Transcriptome sequencing and proteome sequencing were performed on LGBLEL and orbital CH diag nosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between July 2010 and October 2013. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to jointly analyze the differentially expressed ge nes and proteins related to FcεRI signaling pathway. Four LGBLEL and three orbital CH diagnosed by histopathology in Beijing Tongren Hospital, Capital Medical University, between October 2018 and August 2019 were randomly selected as the experimental group and the control group, respectively. RT PCR, immunohistochemical staining, and western blotting were used to verify the genes and proteins related to the FcεRI signaling pathway.Results: Combined transcriptome and proteome analysis showed that the FcεRI signaling pathway was up regulated in LGBLEL (P=0.0040), and that the important proteins such as SYK, p38, JNK, PI3K, and ERK were highly expressed in LGBLEL tissues. RT PCR results showed that the mRNA expression levels of SYK, p38, JNK, PI3K, and ERK wer e significantly increased in the LGBLEL group (P=0.0066, P=0.0002, P=0.0003, P<0.0001, P<0.0001, respectively). Immunohistochemical staining results showed that the protein expression levels of SYK, p38, JNK, PI3K, and ERK in LGBLEL tissues were significan tly higher than in orbital CH. Western Blotting showed that the protein contents of p SYK, p p38, p JNK, p PI3K, and p ERK were significantly higher than in orbital CH (P=0.0169, P=0.0074, P=0.0046, P=0.0157, P=0.0156, respectively). Conclusion: The genes and proteins related to the FcεRI signaling pathway are up regulated in LGBLEL, indicating that the FcεRI signaling pathway participates in the pathogenesis of LGBLEL.

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.