Receptor Functions of Semaphorin 4D

Куклина, Е. М.

doi:10.1134/s0006297919090049

Cited by 11 publications

(9 citation statements)

References 38 publications

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“…For the inversely correlated genes, we validated SEMA4D and VWA1, for which hypomethylation in the promoter region of both genes was associated with gene up regulation in G. parasuis infected porcine brain. SEMA4D is a classic member of the semaphorin family that is widely represented in the immune system and plays an important role in many physiological and pathological processes, including immunoregulation, angiogenesis, neurogenesis, and tumor progression (43,44). It is reported that SEMA4D contributes to the formation of cellular, humoral, and innate immune responses, such as inflammation, immune cell migration, and immunological synapse formation (45).…”

Section: Discussionmentioning

confidence: 99%

Methylome and Transcriptome-Based Integration Analysis Identified Molecular Signatures Associated With Meningitis Induced by Glaesserella parasuis

Li-wei

Chen

et al. 2022

Front. Immunol.

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Glaesserella parasuis (G. parasuis) can elicit serious inflammatory responses and cause meningitis in piglets. Previous epigenetic studies have indicated that alterations in host DNA methylation may modify the inflammatory response to bacterial infection. However, to date, genome-wide analysis of the DNA methylome during meningitis caused by G. parasuis infection is still lacking. In this study, we employed an unbiased approach using deep sequencing to profile the DNA methylome and transcriptome from G. parasuis infected porcine brain (cerebrum) and integrated the data to identify key differential methylation regions/sites involved in the regulation of the inflammatory response. Results showed that DNA methylation patterns and gene expression profiles from porcine brain were changed after G. parasuis infection. The majority of the altered DNA methylation regions were found in the intergenic regions and introns and not associated with CpG islands, with only a low percentage occurring at promoter or exon regions. Integrated analysis of the DNA methylome and transcriptome identified a number of inversely and positively correlated genes between DNA methylation and gene expression, following the criteria of |log2FC| > 0.5, |diffMethy| > 0.1, and P < 0.05. Differential expression and methylation of two significant genes, semaphoring 4D (SEMA4D) and von Willebrand factor A domain containing 1 (VWA1), were validated by qRT-PCR and bisulfite sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses demonstrated that DNA methylation inversely correlated genes in G. parasuis infected porcine brains were mainly involved with cell adhesion molecules (CAMs), bacterial invasion of epithelial cells, RIG-1-like receptor signaling pathways, and hematopoietic cell lineage signaling pathways. In addition, a protein-protein interaction network of differentially methylated genes found potential candidate molecular interactions relevant to the pathology of G. parasuis infection. To the best of our knowledge, this is the first attempt to integrate the DNA methylome and transcriptome data from G. parasuis infected porcine brains. Our findings will help understanding the contribution of genome-wide DNA methylation to the pathogenesis of meningitis in pigs and developing epigenetic biomarkers and therapeutic targets for the treatment of G. parasuis induced meningitis.

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Section: Discussionmentioning

confidence: 99%

Methylome and Transcriptome-Based Integration Analysis Identified Molecular Signatures Associated With Meningitis Induced by Glaesserella parasuis

Li-wei

Chen

et al. 2022

Front. Immunol.

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“…Some evidence of receptor functions of Sema4D has also been reported in non-neuronal cell types 62 , a notable example being in γδ T lymphocytes where antibody-mediated activation of Sema4D resulted in phosphorylation of ERK, dephosphorylation of cofilin and activation of integrins resulting in cell rounding required for wound healing 63 .…”

Section: Discussionmentioning

confidence: 95%

Sema7A and Sema4D Heterodimerization is Essential for Membrane Targeting and Neocortical Wiring

Bessa

Newman

Yan

et al. 2023

Preprint

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Disruption of neocortical circuitry and architecture in humans causes numerous neurodevelopmental disorders. Neocortical cytoarchitecture is orchestrated by various transcription factors such as Satb2 that control target genes during strict time windows. In humans, mutations of SATB2 cause SATB2 Associated Syndrome (SAS), a multisymptomatic syndrome involving intellectual disability, speech delay, epilepsy and craniofacial defects. We show that Satb2 controls neuronal migration and axonal outgrowth by inducing the expression of the GPI-anchored protein, Sema7A. We find that heterodimerization with Sema4D increases targeting of Sema4D to the membrane and is required for Sema7A function. Finally, we report that membrane localization and pos-translational modification of the Sema7A-Sema4D complex is disrupted by a novel de novo mutation in Sema4D (Q497P) that is associated with epilepsy in humans.

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“…As a ligand, membrane or sCD100 binds to CD72 or PLXNB1 and regulates the activation and/or proliferation of immune cells (20)(21)(22) and tumor cells (23), or binds to PLXNB2 and triggers the release of epithelium healing factors (24,25). As a receptor, CD100 acts as a T cell costimulatory molecule (26)(27)(28).…”

Section: Downstream Signaling Alterations Caused By the K849t Mutationmentioning

confidence: 99%

A heterozygous germline CD100 mutation in a family with primary sclerosing cholangitis

et al. 2021

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Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease without clear etiology or effective treatment. Genetic factors contribute to PSC pathogenesis, but so far, no causative mutation has been found. We performed whole-exome sequencing in a family with autosomal dominant inheritance of PSC and identified a heterozygous germline missense mutation in SEMA4D, encoding a K849T variant of CD100. The mutation was located in an evolutionarily conserved, unstructured cytosolic region of CD100 affecting downstream signaling. It was found to alter the function of CD100-expressing cells with a bias toward the T cell compartment that caused increased proliferation and impaired interferon-γ (IFN-γ) production after stimulation. Homologous mutation knock-in mice developed similar IFN-γ impairment in T cells and were more prone to develop severe cholangitis when exposed to 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Transfer of wild-type T cells to knock-in mice before and during DDC exposure attenuated cholangitis. Taken together, we identified an inherited mutation in the disordered cytosolic region of CD100 resulting in T cell functional defects. Our findings suggest a protective role for T cells in PSC that might be used therapeutically.

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Receptor Functions of Semaphorin 4D

Cited by 11 publications

References 38 publications

Methylome and Transcriptome-Based Integration Analysis Identified Molecular Signatures Associated With Meningitis Induced by Glaesserella parasuis

Methylome and Transcriptome-Based Integration Analysis Identified Molecular Signatures Associated With Meningitis Induced by Glaesserella parasuis

Sema7A and Sema4D Heterodimerization is Essential for Membrane Targeting and Neocortical Wiring

A heterozygous germline CD100 mutation in a family with primary sclerosing cholangitis

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