Role of the cytokine BAFF in autoimmune diseases: Physiopathology and therapeutic targets

Ospina, Fabio E.; Betancur, Juan Felipe; Suso, Juan Pablo; Muñoz-Buitrón, Evelyn; Cañas, Carlos A.; Tobón, Gabriel J.

doi:10.1016/j.rcreue.2016.11.003

Cited by 6 publications

(7 citation statements)

References 116 publications

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“…The authors also showed that NET exposure induced phosphorylation of protein kinase B (PKB or AKT), extracellular signal-regulated protein kinase 1/2 (ERK1/2) and p38; the release of IL-8 and B-cell activating factor (BAFF) by neutrophils at 18 h, but not the previously reported cytokine, tumor necrosis factor α (TNFα) [ 93 ]. This auto-amplification loop may lead to excessive release of BAFF, which may result in the generation of autoantibodies [ 94 ], leading to autoimmunity.…”

Section: Pathways To Netosismentioning

confidence: 99%

“…The most recent elucidation of the mechanistic role of NETs in MS pathogenesis was performed by Wilson et al, showing that histones can directly activate T cells for T-helper 17 (Th17) differentiation via TLR2 and myeloid differentiation primary response 88 (MyD88), leading to the phosphorylation of signal transducer and activator of transcription (STAT3) [ 95 ], essential for Th17 cell responses [ 96 ]. Komiyama et al also demonstrated the ability of NETs to activate inflammatory Th17 cells, which can secrete IL-17, a neutrophil chemotaxis cytokine [ 94 ]. Using IL-17−/− mice, the authors showed a significant decrease in immune cell infiltrate, delayed the onset and reduced disease severity [ 94 ], providing a potential therapeutic target for MS treatment.…”

Section: Nets—friend or Foe In Human Disease?mentioning

confidence: 99%

“…Komiyama et al also demonstrated the ability of NETs to activate inflammatory Th17 cells, which can secrete IL-17, a neutrophil chemotaxis cytokine [ 94 ]. Using IL-17−/− mice, the authors showed a significant decrease in immune cell infiltrate, delayed the onset and reduced disease severity [ 94 ], providing a potential therapeutic target for MS treatment. Other groups have demonstrated that pharmaceutical inhibition of MPO reduced oxidative stress and enhanced integrity of the blood–brain barrier (BBB), decreasing disease severity [ 130 , 131 ].…”

Section: Nets—friend or Foe In Human Disease?mentioning

confidence: 99%

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The Expanding Role of Extracellular Traps in Inflammation and Autoimmunity: The New Players in Casting Dark Webs

Huang

O’Sullivan

2022

IJMS

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The first description of a new form of neutrophil cell death distinct from that of apoptosis or necrosis was discovered in 2004 and coined neutrophil extracellular traps “(NETs)” or “NETosis”. Different stimuli for NET formation, and pathways that drive neutrophils to commit to NETosis have been elucidated in the years that followed. Critical enzymes required for NET formation have been discovered and targeted therapeutically. NET formation is no longer restricted to neutrophils but has been discovered in other innate cells: macrophages/monocytes, mast Cells, basophils, dendritic cells, and eosinophils. Furthermore, extracellular DNA can also be extruded from both B and T cells. It has become clear that although this mechanism is thought to enhance host defense by ensnaring bacteria within large webs of DNA to increase bactericidal killing capacity, it is also injurious to innocent bystander tissue. Proteases and enzymes released from extracellular traps (ETs), injure epithelial and endothelial cells perpetuating inflammation. In the context of autoimmunity, ETs release over 70 well-known autoantigens. ETs are associated with pathology in multiple diseases: lung diseases, vasculitis, autoimmune kidney diseases, atherosclerosis, rheumatoid arthritis, cancer, and psoriasis. Defining these pathways that drive ET release will provide insight into mechanisms of pathological insult and provide potential therapeutic targets.

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Section: Pathways To Netosismentioning

confidence: 99%

Section: Nets—friend or Foe In Human Disease?mentioning

confidence: 99%

Section: Nets—friend or Foe In Human Disease?mentioning

confidence: 99%

See 1 more Smart Citation

The Expanding Role of Extracellular Traps in Inflammation and Autoimmunity: The New Players in Casting Dark Webs

Huang

O’Sullivan

2022

IJMS

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“…Nevertheless, NET-induced BAFF secretion by neutrophils suggests, that NETs play an active role in shaping the adaptive immune response, since BAFF is important for the activation of B cells (46). However, excessive release of BAFF is associated with the formation of autoantibodies (47) and an increased release of BAFF induced by NETs could further link NET release to the development of auto-immunity. An important step in the characterization of the NETinduced activation of neutrophils is to identify the receptor engaged by NETs.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Extracellular Traps Activate Proinflammatory Functions of Human Neutrophils

et al. 2021

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Neutrophil extracellular traps (NETs) consist of decondensed nuclear chromatin that is associated with proteins and are released by neutrophils during an inflammatory response. Released NETs are able to capture pathogens, prevent their dissemination and potentially kill them via antimicrobial peptides and proteins that are associated with the decondensed chromatin. In addition to their antimicrobial functions, NETs have also been shown to exert immunomodulatory effects by activation and differentiation of macrophages, dendritic cells and T cells. However, the effect of NETs on neutrophil functions is poorly understood. Here we report the first comprehensive study regarding the effects of NETs on human primary neutrophils in vitro. NETs were isolated from cultures of PMA-exposed neutrophils. Exposure of neutrophils to isolated NETs resulted in the activation of several neutrophil functions in a concentration-dependent manner. NETs induced exocytosis of granules, the production of reactive oxygen species (ROS) by the NADPH oxidase NOX2, NOX2-dependent NET formation, increased the phagocytosis and killing of microbial pathogens. Furthermore, NETs induced the secretion of the proinflammatory chemokine IL-8 and the B-cell-activating cytokine BAFF. We could show that the NET-induced activation of neutrophils occurs by pathways that involve the phosphorylation of Akt, ERK1/2 and p38. Taken together our results provide further insights into the proinflammatory role of NETs by activating neutrophil effector function and further supports the view that NETs can amplify inflammatory events. On the one hand the amplified functions enhance the antimicrobial defense. On the other hand, NET-amplified neutrophil functions can be involved in the pathophysiology of NET-associated diseases. In addition, NETs can connect the innate and adaptive immune system by inducing the secretion of the B-cell-activating cytokine BAFF.

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“…This cytokine has been demonstrated to induce B cell survival (Moore et al, 1999 ), proliferation (Schneider et al, 1999 ), maturation (Schneider et al, 2001 ), extrafollicular responses (MacLennan & Vinuesa, 2002 ), and T‐independent class‐switch recombination (Castigli et al, 2005 ). Multiple studies had associated high levels of sBAFF with several autoimmune diseases, being SLE one of the most consistently associated (Ospina et al, 2016 ). BAFF is encoded TNFSF13B gene and several SNPs have been reported in association with increased risk for ADs (Gottenberg et al, 2006 ; Kawasaki et al, 2002 ; Nezos et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of TNFSF13B polymorphisms and BAFF expression in rheumatoid arthritis and primary Sjögren's syndrome patients

Santillán-López

Muñoz‐Valle

Edith

et al. 2022

Molec Gen & Gen Med

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Background:The increased expression of B cell-activating factor (BAFF) has been linked to autoantibody production in autoimmune diseases (ADs). The aim of this study was to investigate the association among TNFSF13B gene (OMIM: 603969) single nucleotide polymorphisms (SNPs), TNFSF13B mRNA, and soluble BAFF (sBAFF) expression in patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). The diagnostic value of sBAFF also was evaluated by the area under the curve (AUC) of receiver operating characteristic or receptor (ROC) curves. Methods: Genotypes of the TNFSF13B rs9514827 (−2841 T > C), rs1041569 (−2701 A > T) and rs9514828 (−871 C > T) SNPs were determined by PCR-RFLP assay. TNFSF13B mRNA and sBAFF expression were performed by RT-qPCR and ELISA, respectively. The study included 320 RA patients, 101 pSS patients, and 309 healthy subjects (HS).Results: The rs9514828 T allele and the TAT haplotype were associated with an increased risk to develop RA. In both ADs, the TNFSF13B mRNA levels were

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Role of the cytokine BAFF in autoimmune diseases: Physiopathology and therapeutic targets

Cited by 6 publications

References 116 publications

The Expanding Role of Extracellular Traps in Inflammation and Autoimmunity: The New Players in Casting Dark Webs

The Expanding Role of Extracellular Traps in Inflammation and Autoimmunity: The New Players in Casting Dark Webs

Neutrophil Extracellular Traps Activate Proinflammatory Functions of Human Neutrophils

Analysis of TNFSF13B polymorphisms and BAFF expression in rheumatoid arthritis and primary Sjögren's syndrome patients

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