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| Open AccessEtrolizumab-s fails to control E-Cadherin-dependent co-stimulation of highly activated cytotoxic T cells
The clinical success of anti- αEβ7 antibody Etrolizumab for Crohn’s disease is less than what is expected based on proof-of-concept studies. Here authors show, by characterization of T cells from Etrolizumab-treated patients, in vitro functional assays and reanalysis of public single cell datasets on Etrolizumab-treated patients, that at high level of T cell activation, which characterises T cells in Crohn’s disease, E-Cadherin-αEβ7 interactions become resistant to Etrolizumab inhibition.
- Maximilian Wiendl
- , Mark Dedden
- & Sebastian Zundler
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Article
| Open AccessMechanism of integrin activation by talin and its cooperation with kindlin
The authors report here that talin and kindlin, the two key integrin binders and activators, are bridged by paxillin to induce microclustering of integrins to potently bind to multivalent extracellular ligand and trigger rapid cell attachment.
- Fan Lu
- , Liang Zhu
- & Jun Qin
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Article
| Open AccessArf6-driven cell invasion is intrinsically linked to TRAK1-mediated mitochondrial anterograde trafficking to avoid oxidative catastrophe
Mitochondria subcellular localization is dynamically regulated during migration. Here, the authors show that Arf6–AMAP1 dependent ILK localization at focal adhesions reduces mitochondrial retrograde trafficking in migratory cells and prevents mitochondrial aggregation and detrimental ROS production.
- Yasuhito Onodera
- , Jin-Min Nam
- & Hisataka Sabe
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Article
| Open AccessIntegrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells
Smooth muscle cells (SMCs) invade atherosclerotic lesions and expand, contributing to plaque progression. Here Misra et al. show that SMC-derived plaque cells come from a single SMC and integrin β3 in SMCs and macrophages regulate the fate, expansion and migration of SMCs during plaque formation.
- Ashish Misra
- , Zhonghui Feng
- & Daniel M. Greif
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Article
| Open AccessDirection of actin flow dictates integrin LFA-1 orientation during leukocyte migration
Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here the authors show that actin flow can orient cell surface integrins during leukocyte migration, suggesting integrin activation by cytoskeletal force.
- Pontus Nordenfelt
- , Travis I. Moore
- & Timothy A. Springer
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Article
| Open Accessαv integrins on mesenchymal cells regulate skeletal and cardiac muscle fibrosis
The mechanisms underlying tissue fibrosis are unclear. The authors show that mesenchymal cells expressing PDGFRβ mediate fibrosis in skeletal muscle and heart via a mechanism involving αv integrin, and that inhibitors of αv integrins attenuate fibrotic responses in mice.
- I. R. Murray
- , Z. N. Gonzalez
- & N. C. Henderson
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Article
| Open AccessCoordinated integrin activation by actin-dependent force during T-cell migration
The role of force in activating integrin cell adhesion receptors is not known. Here the authors develop fluorescent tension sensors for αL and β2 integrins and show that in migrating T cells force is transduced across the β2 integrin, and that this correlates with an active conformational state.
- Pontus Nordenfelt
- , Hunter L. Elliott
- & Timothy A. Springer