The role of semaphorins in immune responses and autoimmune rheumatic diseases

Nishide, Masayuki; Kumanogoh, Atsushi

doi:10.1038/nrrheum.2017.201

Cited by 105 publications

(87 citation statements)

References 80 publications

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“…These alternatively activated macrophages could produce a significant amount of ADAM‐17 inducing the shedding of Sema7A. This in turn could stimulate monocytes . In agreement with this hypothesis, we showed a clear relationship between the levels of Sema7A and CCL‐18, which is considered as a biomarker of the Gaucher cell mass.…”

Section: Discussionsupporting

confidence: 88%

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Semaphorin 7A: A novel marker of disease activity in Gaucher disease

et al. 2020

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Gaucher disease (GD) is a recessively inherited lysosomal storage disorder in which sphingolipids accumulates in the macrophages that transform into Gaucher cells. A growing body of evidence indicates that red blood cells (RBCs) represent important actors in GD pathophysiology. We previously demonstrated that altered RBC properties including increased Lyso-GL1 levels, dyserythropoiesis, and iron metabolism defect in GD patients contribute to anemia and hyperferritinemia. Since RBC defects also correlated well with markers of GD severity and were normalized under enzyme replacement therapy (ERT), the identification of molecules that are deregulated in GD RBCs represents an important issue in the search of pertinent markers of the disease.

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Section: Discussionsupporting

confidence: 88%

“…The biological effects of Sema7A have been reported with both the soluble and the membrane forms . In our study, the decrease in membrane Sema7A in RBCs from GD patients strongly suggests that these cells are most likely the main source of soluble Sema7A.…”

Section: Discussionsupporting

confidence: 58%

Semaphorin 7A: A novel marker of disease activity in Gaucher disease

et al. 2020

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“…The semaphorin family is a large group of proteins initially described as axonal guidance molecules, but now appreciated for their roles in other physiologic and pathologic processes, including the regulation of immune responses, angiogenesis, cell migration, and tissue invasion . Semaphorin 4A (Sema4A) is a transmembrane protein that can also be cleaved and released into circulation.…”

Section: Introductionmentioning

confidence: 99%

Induction of Inflammation and Fibrosis by Semaphorin 4A in Systemic Sclerosis

Carvalheiro

Affandi

Malvar‐Fernández

et al. 2019

Arthritis & Rheumatology

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Objective To analyze the potential role of semaphorin 4A (Sema4A) in inflammatory and fibrotic processes involved in the pathology of systemic sclerosis (SSc). Methods Sema4A levels in the plasma of healthy controls (n = 11) and SSc patients (n = 20) were determined by enzyme‐linked immunosorbent assay (ELISA). The expression of Sema4A and its receptors in monocytes and CD4+ T cells from healthy controls and SSc patients (n = 6–7 per group) was determined by ELISA and flow cytometry. Th17 cytokine production by CD4+ T cells (n = 5–7) was analyzed by ELISA and flow cytometry. The production of inflammatory mediators and extracellular matrix (ECM) components by dermal fibroblast cells (n = 6) was analyzed by quantitative polymerase chain reaction, ELISA, Western blotting, confocal microscopy, and ECM deposition assay. Results Plasma levels of Sema4A, and Sema4A expression by circulating monocytes and CD4+ T cells, were significantly higher in SSc patients than in healthy controls (P < 0.05). Inflammatory mediators significantly up‐regulated the secretion of Sema4A by monocytes and CD4+ T cells from SSc patients (P < 0.05 versus unstimulated SSc cells). Functional assays showed that Sema4A significantly enhanced the expression of Th17 cytokines induced by CD3/CD28 in total CD4+ T cells as well in different CD4+ T cell subsets (P < 0.05 versus unstimulated SSc cells). Finally, Sema4A induced a profibrotic phenotype in dermal fibroblasts from both healthy controls and SSc patients, which was abrogated by blocking or silencing the expression of Sema4A receptors. Conclusion Our findings indicate that Sema4A plays direct and dual roles in promoting inflammation and fibrosis, 2 main features of SSc, suggesting that Sema4A might be a novel therapeutic target in SSc.

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“…Gene g227 encodes a trans-membrane semaphorin 1A (Sema1A)-like protein (Class 1 semaphorins). While semaphorins generally act as signaling ligands that regulate the shape and motility of cells, their roles in immunity have been noticed [75,76]. Membrane-associated semaphorins play a role in regulating immune homeostasis in mouse models [77], according to which CD72 (Cluster of Differentiation 72) and TIM-2 (T cell immunoglobulin and mucin domain protein 2) ligands functionally interact with semaphorin Sema4D and Sema4A, respectively [78].…”

Section: Nimav-1_lva Genes Involved In Host-pathogen Interactionmentioning

confidence: 99%

The Complete Genome of an Endogenous Nimavirus (Nimav-1_LVa) From the Pacific Whiteleg Shrimp Penaeus (Litopenaeus) Vannamei

Bao

Tang

Alcivar–Warren³

2020

Genes

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White spot syndrome virus (WSSV), the lone virus of the genus Whispovirus under the family Nimaviridae, is one of the most devastating viruses affecting the shrimp farming industry. Knowledge about this virus, in particular, its evolution history, has been limited, partly due to its large genome and the lack of other closely related free-living viruses for comparative studies. In this study, we reconstructed a full-length endogenous nimavirus consensus genome, Nimav-1_LVa (279,905 bp), in the genome sequence of Penaeus (Litopenaeus) vannamei breed Kehai No. 1 (ASM378908v1). This endogenous virus seemed to insert exclusively into the telomeric pentanucleotide microsatellite (TAACC/GGTTA)n. It encoded 117 putative genes, with some containing introns, such as g012 (inhibitor of apoptosis, IAP), g046 (crustacean hyperglycemic hormone, CHH), g155 (innexin), g158 (Bax inhibitor 1 like). More than a dozen Nimav-1_LVa genes are involved in the pathogen-host interactions. We hypothesized that g046, g155, g158, and g227 (semaphorin 1A like) were recruited host genes for their roles in immune regulation. Sequence analysis indicated that a total of 43 WSSV genes belonged to the ancestral/core nimavirus gene set, including four genes reported in this study: wsv112 (dUTPase), wsv206, wsv226, and wsv308 (nucleocapsid protein). The availability of the Nimav-1_LVa sequence would help understand the genetic diversity, epidemiology, evolution, and virulence of WSSV.

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The role of semaphorins in immune responses and autoimmune rheumatic diseases

Cited by 105 publications

References 80 publications

Semaphorin 7A: A novel marker of disease activity in Gaucher disease

Semaphorin 7A: A novel marker of disease activity in Gaucher disease

Induction of Inflammation and Fibrosis by Semaphorin 4A in Systemic Sclerosis

The Complete Genome of an Endogenous Nimavirus (Nimav-1_LVa) From the Pacific Whiteleg Shrimp Penaeus (Litopenaeus) Vannamei

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