Search

BackgroundDermatomyositis is an autoimmune disease characterized by damage to the skin and muscles. CD4+ T cells are of crucial importance in the occurrence and development of dermatomyositis (DM). However, there are few bioinformatics studies on potential pathogenic genes and immune cell infiltration of DM. Therefore, this study intended to explore CD4+ T-cell infiltration–associated key genes in DM and construct a new model to predict the level of CD4+ T-cell infiltration in DM.MethodsGSE46239, GSE142807, GSE1551, and GSE193276 datasets were downloaded. The WGCNA and CIBERSORT algorithms were performed to identify the most correlated gene module with CD4+ T cells. Matascape was used for GO enrichment and KEGG pathway analysis of the key gene module. LASSO regression analysis was used to identify the key genes and construct the prediction model. The correlation between the key genes and CD4+ T-cell infiltration was investigated. GSEA was performed to research the underlying signaling pathways of the key genes. The key gene-correlated transcription factors were identified through the RcisTarget and Gene-motif rankings databases. The miRcode and DIANA-LncBase databases were used to build the lncRNA-miRNA-mRNA network.ResultsIn the brown module, 5 key genes (chromosome 1 open reading frame 106 (C1orf106), component of oligomeric Golgi complex 8 (COG8), envoplakin (EVPL), GTPases of immunity-associated protein family member 6 (GIMAP6), and interferon-alpha inducible protein 6 (IFI6)) highly associated with CD4+ T-cell infiltration were identified. The prediction model was constructed and showed better predictive performance in the training set, and this satisfactory model performance was validated in another skin biopsy dataset and a muscle biopsy dataset. The expression levels of the key genes promoted the CD4+ T-cell infiltration. GSEA results revealed that the key genes were remarkably enriched in many immunity-associated pathways, such as JAK/STAT signaling pathway. The cisbp_M2205, transcription factor-binding site, was enriched in C1orf106, EVPL, and IF16. Finally, 3,835 lncRNAs and 52 miRNAs significantly correlated with key genes were used to build a ceRNA network.ConclusionThe C1orf106, COG8, EVPL, GIMAP6, and IFI6 genes are associated with CD4+ T-cell infiltration. The prediction model constructed based on the 5 key genes may better predict the level of CD4+ T-cell infiltration in damaged muscle and lesional skin of DM. These key genes could be recognized as potential biomarkers and immunotherapeutic targets of DM.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease (CTD), the main features of which are multiple serum autoantibodies and extensive involvement of multiple systems. The onset age of patients varies from childhood to middle age, with nearly 1/5 in childhood. Sjogren’s syndrome (SS) is also an autoimmune disease characterized by high-degree lymphocytic infiltration of exocrine glands, usually occurring in middle-aged and older women, and rarely in childhood. Neuromyelitis optica spectrum disorder (NMOSD) is an immune-mediated inflammatory demyelinating disease of the central nervous system (CNS) mainly involving the optic nerve and spinal cord. The coexistence of NMOSD and SLE and/or SS is well recognized by both neurologists and rheumatologists, but cases in children have been rarely reported. In this paper, we reported a case of a girl with onset at age 5 clinically featured by recurrent parotid gland enlargement, pancytopenia, hypocomplementemia, multiple positive serum antibodies, and cirrhosis. She was initially diagnosed with SS/SLE overlap syndrome at age 5. Four years later, the patient suffered a sudden vision loss and was examined to have positive AQP4 antibodies in serum and cerebrospinal fluid (CSF), and long segmental spinal swelling, in line with the diagnostic criteria for NMOSD. Up to now, the current patient is of the youngest onset age to develop SS/SLE coexisting with NMOSD, also with cirrhosis. It is important for clinicians to be aware of the possibility of CTDs coexisting with NMOSD in children, especially in those with positive anti-multiple autoantibodies, and to decrease the rate of missed diagnosis.

Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) is critical for the pathogenesis of Escherichia coli (E. coli) K1 meningitis, a severe central nervous system infection of the neonates. However, little is known about how E. coli K1 manipulates α7 nAChR signaling. Here, through employing immortalized cell lines, animal models, and human transcriptional analysis, we showed that E. coli K1 infection triggers releasing of secreted Ly6/Plaur domain containing 1 (SLURP1), an endogenous α7 nAChR ligand. Exogenous supplement of SLURP1, combined with SLURP1 knockdown or overexpression cell lines, showed that SLURP1 is required for E. coli K1 invasion and neutrophils migrating across the blood-brain barrier (BBB). Furthermore, we found that SLURP1 is required for E. coli K1-induced α7 nAChR activation. Finally, the promoting effects of SLURP1 on the pathogenesis of E. coli K1 meningitis was significantly abolished in the α7 nAChR knockout mice. These results reveal that E. coli K1 exploits SLURP1 to activate α7 nAChR and facilitate its pathogenesis, and blocking SLURP1-α7 nAChR interaction might represent a novel therapeutic strategy for E. coli K1 meningitis.

Nucleotide oligomerization domain-like receptors (NLRs), a class of pattern recognition receptors, participate in the host’s first line of defense against invading pathogenic microorganisms. NLR family caspase recruitment domain containing 5 (NLRC5) is the largest member of the NLR family and has been shown to play an important role in inflammatory processes, angiogenesis, immunity, and apoptosis by regulating the nuclear factor-κB, type I interferon, and inflammasome signaling pathways, as well as the expression of major histocompatibility complex I genes. Recent studies have found that NLRC5 is also associated with neuronal development and central nervous system (CNS) diseases, such as CNS infection, cerebral ischemia/reperfusion injury, glioma, multiple sclerosis, and epilepsy. This review summarizes the research progress in the structure, expression, and biological characteristics of NLRC5 and its relationship with the CNS.