TLR9/FCRL3 regulates B cell viability, apoptosis, and antibody and IL-10 production through ERK1/2, p38, and STAT3 signaling pathways

Liu, Qi-Bing; Zhou, RenHui; Liu, Chong-Mei

doi:10.1007/s11626-022-00720-8

Cited by 2 publications

(1 citation statement)

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“…In humans, FCRL3 encodes a type I transmembrane protein prominently expressed in lymphoid organs, where it assumes a pivotal role in the early stages of B-cell maturation and subsequent activation ( 17 , 18 ). Given the integral involvement of B cells in MS progression and their close association with FCRL3 ( 19 ), TLR9 activation affects B cell proliferation, apoptosis, antibody production, and IL-10 secretion by upregulating FCRL3 expression, FCRL3 can activate the SHP-1 and p38 MAPK pathways and then promote the secretion of IL-10 in B cells, thus inhibiting the secretion of inflammatory factors ( 19 , 20 ). Therefore, FCRL3 may play an immunoprotective role in MS, and it will be an effective target for the diagnosis and treatment of MS. Several investigations have implicated FCRL3 and its functional promoter polymorphism -169 T/C in the pathogenesis of various autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, and autoimmune thyroid diseases ( 18 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated analyses of single-cell transcriptome and Mendelian randomization reveal the protective role of FCRL3 in multiple sclerosis

Yu,

Jiang,

et al. 2024

Front. Immunol.

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BackgroundMultiple sclerosis (MS) represents a multifaceted autoimmune ailment, prompting the development and widespread utilization of numerous therapeutic interventions. However, extant medications for MS have proven inadequate in mitigating relapses and halting disease progression. Innovative drug targets for preventing multiple sclerosis are still required. The objective of this study is to discover novel therapeutic targets for MS by integrating single-cell transcriptomics and Mendelian randomization analysis.MethodsThe study integrated MS genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data for analysis and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and MS. Sequential analyses involving colocalization and Phenome-wide association studies (PheWAS) were conducted to validate the causal role of candidate genes.ResultsFollowing stringent quality control preprocessing of scRNA-seq data, 1,123 expression changes across seven peripheral cell types were identified. Among the seven most prevalent cell types, 97 genes exhibiting at least one eQTL were discerned. Examination of MR associations between 28 proteins with available index pQTL signals and the risk of MS outcomes was conducted. Co-localization analyses and PheWAS indicated that FCRL3 may exert influence on MS.ConclusionThe integration of scRNA-seq and MR analysis facilitated the identification of potential therapeutic targets for MS. Notably, FCRL3, implicated in immune function, emerged as a significant drug target in the deCODE databases. This research underscores the importance of FCRL3 in MS therapy and advocates for further investigation and clinical trials targeting FCRL3.

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