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| Open AccessBAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus
Blocking B-cell activating factor (BAFF), an important soluble factor for B-cell responses, with specific antibodies is approved for treating autoimmune disorders. Here the authors show, with structural data, that antibody-BAFF interactions not only interrupt BAFF–receptor-binding, but also induce the formation of a less active BAFF polymer.
- Woori Shin
- , Hyun Tae Lee
- & Yong-Seok Heo
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Article
| Open AccessA loop region of BAFF controls B cell survival and regulates recognition by different inhibitors
BAFF is an important cytokine for B cell survival, and is a therapeutic target for autoimmune disorders. Here the authors show that a 'flap' region of BAFF converts BAFFR binding events into survival signals and, with structural data, that this ‘flap’ differentially modulates binding of drugs such as belimumab or atacicept.
- Michele Vigolo
- , Melissa G. Chambers
- & Pascal Schneider
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| Open AccessProstaglandin D2 amplifies lupus disease through basophil accumulation in lymphoid organs
In a lupus environment, basophils accumulate in secondary lymphoid organs where they affect pathogenesis by stimulating autoantibody production. Here the authors show this accumulation is driven by PGD2-induced CXCR4 surface expression and trafficking of basophils.
- Christophe Pellefigues
- , Barbara Dema
- & Nicolas Charles
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Article
| Open AccessA ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense
Integrin-based therapeutics could block inflammatory processes but they also impair host defence, limiting their usefulness. Here the authors report an anti-Mac1 antibody that blocks its interaction with pro-inflammatory ligand CD40L but not other ligands, and show that it can protect against sepsis in mice.
- Dennis Wolf
- , Nathaly Anto-Michel
- & Andreas Zirlik
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| Open AccessRegulatory T cells control toxicity in a humanized model of IL-2 therapy
High dose IL-2 is a viable treatment option for cancer immune therapy, but the underlying mechanism for the accompanying undesirable morbidity is unclear. Here the authors show, using human immune system mouse models, that regulatory T cells and their functions on effector T cells are essential modulators of the related pathogenesis.
- Yan Li
- , Helene Strick-Marchand
- & James P. Di Santo
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Article
| Open AccessUnique transcriptome signatures and GM-CSF expression in lymphocytes from patients with spondyloarthritis
Spondyloarthritis is an inflammatory disease with Th17 cells implicated in the pathogenesis. Here the authors show that patients with spondyloarthritis have increased numbers of GM-CSF-secreting blood and synovial lymphocytes, Th17 or not, that carry a unique transcriptional profile including enhanced GPR65 expression.
- M. H. Al-Mossawi
- , L. Chen
- & P. Bowness
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Article
| Open AccessSomatic mutations in clonally expanded cytotoxic T lymphocytes in patients with newly diagnosed rheumatoid arthritis
Accumulation of somatic mutations in lymphocytes is a feature of some cancers. Here the authors show that patients with recent onset of rheumatoid arthritis also accumulate mutations in their expanded CD8+ effector memory T cell pool independent of cancer association.
- P. Savola
- , T. Kelkka
- & S. Mustjoki
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| Open AccessEfficient ex vivo analysis of CD4+ T-cell responses using combinatorial HLA class II tetramer staining
Detection of antigen specificity in a blood sample is limited by low frequencies of individual clones. Here the authors develop an MHC class II combinatorial technique and apply it to immunophenotype human CD4+ T cells of multiple specificities in response to influenza vaccine in single blood samples.
- Hannes Uchtenhagen
- , Cliff Rims
- & Eddie A. James