The Fc\u03b5RI signaling pathway is involved in the pathogenesis of lacrimal gland benign lymphoepithelial lesions as shown by transcriptomic analysis

Jing Li,Rui Liu,Nan Wang,Xuan Zhang,Mei Sun,Xin Ge,Jianmin Ma,Jinjin Wang

doi:10.1038/s41598-021-01395-z

Jing Li, Rui Liu + Show 6 more

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https://doi.org/10.1038/s41598-021-01395-z

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Abstract

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.

Highlights

This study aimed to analyze the role of the FcepsilonRI (FcεRI) signaling pathway in the pathogenesis of benign lymphoepithelial lesion of lacrimal gland (LGBLEL)
Compared with the cavernous hemangioma (CH) group, the downregulated differentially expressed genes (DEGs) in the Lacrimal gland benign lymphoepithelial lesion (LGBLEL) group were primarily related to biological processes associated with development-associated signaling processes, including signal transduction, cell adhesion and differentiation, while the upregulated DEGs were primarily associated with immune signaling functions, including immune response, regulation of immune response, as well as T cell and B cell activation (Fig. 2B,C)
LGBLEL is a chronic inflammatory disease, which clinical studies have indicated may be related to diseases including sinusitis and allergic rhinitis

Summary

Introduction

This study aimed to analyze the role of the FcepsilonRI (FcεRI) signaling pathway in the pathogenesis of benign lymphoepithelial lesion of lacrimal gland (LGBLEL). 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). Abbreviations LGBLEL Lacrimal gland benign lymphoepithelial lesions FcεRI FcepsilonRI CH Cavernous hemangioma IL Interleukin Th2 Helper T2 FDR False discovery rate DEGs Differentially expressed genes GO Gene ontology KEGG Kyoto encyclopedia of genes and genomes DAVID Database for Annotation, Visualization and Integrated Discovery IgG4-ROD IgG4-related ocular disease RT-PCR Reverse transcription polymerase chain reaction SYK Spleen tyrosine kinase p38 Mitogen-activated protein kinase, MAPK JNK C-Jun N-terminal kinase PI3K Phosphoinositide 3-kinase ERK Extracellular signal-regulated kinases. We hypothesize that the IgE-mediated FcεRI signaling pathway may be involved in the pathogenesis of LGBLEL

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