The Role of TLR4 on B Cell Activation and Anti-<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="bold-italic">β</mml:mi></mml:mrow><mml:mrow><mml:mn mathvariant="bold-italic">2</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math>GPI Antibody Production in the Antiphospholipid Syndrome

Cheng, Si; Wang, Haibo; Zhou, Hong

doi:10.1155/2016/1719720

Cited by 20 publications

(13 citation statements)

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“…RNA‐seq technology also led to the discovery that liver B cells from neonatal RRV‐BA mice have activation of multiple innate immune pathways, including up‐regulation of TLR4 and TLR7/9. It was recently shown that TLR4 activation plays a key role in promoting the maturation of immature and transitional B cells . Recognition of nucleic acids (NAs) by TLRs 7 and 9 on B cells results in aberrant B‐cell activation, with subsequent production of proinflammatory cytokines .…”

Section: Discussionmentioning

confidence: 99%

“…It was recently shown that TLR4 activation plays a key role in promoting the maturation of immature and transitional B cells. (44) Recognition of nucleic acids (NAs) by TLRs 7 and 9 on B cells results in aberrant B-cell activation, with subsequent production of proinflammatory cytokines. (21,45) Potential NAs stimulating B cells in murine BA may include microbially derived NAs (i.e., RRV) or endogenous NAs from damaged bile duct epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

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Cytokine‐Producing B Cells Promote Immune‐Mediated Bile Duct Injury in Murine Biliary Atresia

et al. 2018

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Biliary atresia (BA) is a neonatal T cell-mediated, inflammatory, sclerosing cholangiopathy. In the rhesus rotavirus (RRV)-induced neonatal mouse model of BA (murine BA), mice lacking B cells do not develop BA, and the lack of B cells is associated with loss of T-cell and macrophage activation. The aim of this study was to determine the mechanism of B cell-mediated immune activation (antigen presentation versus cytokine production) in murine BA. Normal neonatal B cells in the liver are predominantly at pro-B and pre-B cellular development. However, BA mice exhibit a significant increase in the number and activation status of mature liver B cells. Adoptively transferred B cells into RRV-infected, B cell-deficient mice were able to reinstate T-cell and macrophage infiltration and biliary injury. Nonetheless, neonatal liver B cells were incompetent at antigen presentation to T cells. Moreover, 3-83 immunoglobulin transgenic mice, in which B cells only present an irrelevant antigen, developed BA, indicating a B-cell antigen-independent mechanism. B cells from BA mice produced a variety of innate and adaptive immune cytokines associated with immune activation. In vitro trans-well studies revealed that BA B cells secreted cytokines that activated T cells based on increased expression of T-cell activation marker cluster of differentiation 69. Conclusion: Neonatal liver B cells are highly activated in murine BA and contribute to immune activation through production of numerous cytokines involved in innate and adaptive immunity; this work provides increased knowledge on the capacity of neonatal B cells to contribute to an inflammatory disease through cytokine-mediated mechanisms, and future studies should focus on targeting B cells as a therapeutic intervention in human BA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytokine‐Producing B Cells Promote Immune‐Mediated Bile Duct Injury in Murine Biliary Atresia

et al. 2018

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“…The activation of TLR4 in intestinal epithelial cells not only induces the activation of NF‐kB, but also leads to increased cell apoptosis, which results in the loss of intestinal integrity . In addition, TLR4 is also expressed on immune cells including dendritic cells, macrophages, B cells, and T cells . The over‐activation of TLR4 in these cells is strongly associated with immune dysfunction and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Alterations in the gut barrier and involvement of Toll‐like receptor 4 in murine postoperative ileus

Lin

Zhang

Shen

et al. 2018

Neurogastroenterology Motil

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“…The “second hit” relates to an additional factor that further exacerbates a pro-thrombotic state (for example inflammation), which in combination with aPL antibodies ultimately induces thrombosis ( 19 ). The theory of a “second hit” is further supported by recent studies, which have implicated Toll Like Receptors (TLR) in mediating the inflammatory response in the pathogenesis of APS ( 20 , 21 ). However, in the context of pediatric APS, there is a notable absence of other classical pro-thrombotic risk factors including both pathological states (such as hypertension) and lifestyle related factors such as smoking.…”

Section: Pathogenesis Of Apsmentioning

confidence: 96%

The Differences Between Childhood and Adult Onset Antiphospholipid Syndrome

Wincup

Ioannou

2018

Front. Pediatr.

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Antiphospholipid syndrome (APS) is a rare autoimmune disease of unknown etiology that represents a leading cause of acquired thromboembolism and recurrent miscarriage. It is characterized by the persistent elevated presence of pathogenic antiphospholipid auto-antibodies directed against cardiolipin, ß2-glycoprotein-I, and/or a positive lupus anticoagulant test. As with many autoimmune disorders, the pathogenesis of APS is believed to be the result of a complex interaction between environmental triggers and genetic predisposition. Although more common in adults, APS occasionally manifests in the neonatal period and throughout childhood. Adut-onset APS classification criteria are poorly validated to the pediatric population (in which pregnancy related complications are seldom seen) and as a result, assessment of the prevalence of the disease in childhood is difficult. Thromboembolic events seen in children include deep venous thrombosis in addition to stroke and pulmonary embolism, which can lead to significant long-term disability. The disease can be classified as either primary (when occurring in isolation) or secondary, in which the disease is diagnosed in the context of another underlying disease, most commonly systemic lupus erythematosus. A variety of laboratory and clinical difference are seen between pediatric and adult-onset APS. The marked female predominance seen in adult-onset disease is less evident in childhood where the gender split is more evenly spread. In addition, children with APS are at a higher risk of recurrent thromboembolism than adults. The treatment of childhood-onset APS is challenging due to a lack of large-scale prospective studies in the pediatric population. Therapeutic options are often based upon treatment guidelines that have been based upon literature from the adult-onset form of the disease. In the majority of cases, treatment is focused on the prevention of further thrombosis through treatment with long-term anti-coagulation therapy. The evidence for the use of antiplatelet agents (such as aspirin) and hydroxychloroquine is inconclusive. It is important to remember that anti-coagulation can have significant lifestyle implications for the child with APS and it is essential to consider potential implications relating to school and recreational activities, with contact sports often discouraged due to the increased risk of bleeding.

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The Role of TLR4 on B Cell Activation and Anti-β2GPI Antibody Production in the Antiphospholipid Syndrome

Cited by 20 publications

References 98 publications

Cytokine‐Producing B Cells Promote Immune‐Mediated Bile Duct Injury in Murine Biliary Atresia

Cytokine‐Producing B Cells Promote Immune‐Mediated Bile Duct Injury in Murine Biliary Atresia

Alterations in the gut barrier and involvement of Toll‐like receptor 4 in murine postoperative ileus

The Differences Between Childhood and Adult Onset Antiphospholipid Syndrome

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