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| Open AccessCD4+ T cells are activated in regional lymph nodes and migrate to skin to initiate lymphedema
CD4+ T cells are critical for the development of lymphedema. Here the authors show how these cells contribute to lymphedema and identify that the sphingosine-1-phosphate receptor modulator FTY720 can prevent lymphedema in a mouse tail injury model by blocking the release of CD4+ T cells from the lymph nodes to the skin.
- Gabriela D. García Nores
- , Catherine L. Ly
- & Babak J. Mehrara
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Article
| Open AccessCathelicidins prime platelets to mediate arterial thrombosis and tissue inflammation
Cathelicidins are antimicrobial peptides that eliminate pathogens and contribute to the innate immune response. Here the authors show that neutrophil-derived LL-37/CRAMP induces platelet activation and promotes arterial thrombosis and thrombo-inflammation.
- Joachim Pircher
- , Thomas Czermak
- & Christian Schulz
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| Open AccessPolyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease
In vivo imaging of inflammation is crucial for detection and monitoring of many pathologies and noninvasive macrophage quantification has been suggested as a possible approach. Here Keliher et al. describe novel polyglucose nanoparticle tracers that are rapidly excreted by the kidney and with high affinity for macrophages in atherosclerotic plaques.
- Edmund J. Keliher
- , Yu-Xiang Ye
- & Matthias Nahrendorf
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| Open AccessLimited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization
The presence of long-lived memory IgA-producing B cells in the intestine has been difficult to document. Here the authors show that these cells can be induced by oral but not systemic immunization in mice, and characterize unique features that distinguish them from IgA plasma cells.
- Mats Bemark
- , Helena Hazanov
- & Nils Y. Lycke
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| Open AccessExperimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells
Pertussis toxin enhances the induction of autoreactive T cells in mouse models of autoimmunity. Here the authors show that stimulation of IL-1β production in myeloid cells by pertussis toxin is necessary to prime pathogenic Th1/Th17 cells in experimental autoimmune encephalopathy.
- Francesca Ronchi
- , Camilla Basso
- & Federica Sallusto
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| Open AccessLarge-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming
Platelets are blood circulating corpuscles generated from megakaryocytes that initiate wound healing. Here, Moreau et al. describe a way of producing large quantities of megakaryocytes from human pluripotent stem cells in the laboratory, moving us a step closer to manufacturing transfusion products.
- Thomas Moreau
- , Amanda L. Evans
- & Cedric Ghevaert
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| Open AccessEndomucin prevents leukocyte–endothelial cell adhesion and has a critical role under resting and inflammatory conditions
Endomucin is expressed by endothelial cells that line postcapillary venules—the site of leukocyte recruitment during inflammation. Zahr et al.show that endomucin is an anti-adhesive molecule that is downregulated by the cytokine TNF-a and thereby helps in the transition from a quiescent to a pro-adhesive inflamed endothelium.
- Alisar Zahr
- , Pilar Alcaide
- & Pablo Argüeso
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| Open AccessThe transcriptional landscape of age in human peripheral blood
Ageing increases the risk of many diseases. Here the authors compare blood cell transcriptomes of over 14,000 individuals and identify a set of about 1,500 genes that are differently expressed with age, shedding light on transcriptional programs linked to the ageing process and age-associated diseases.
- Marjolein J. Peters
- , Roby Joehanes
- & Andrew D. Johnson
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Article
| Open AccessPannexin 1 channels regulate leukocyte emigration through the venous endothelium during acute inflammation
Endothelial cell activation by inflammation requires extracellular ATP release. Here the authors show that TNF-α induces Src-family kinase-dependent ATP release by Pannexin1 channels in endothelial cells, and that Pannexin1 is required for leukocyte adhesion and emigration into the inflamed tissue.
- Alexander W. Lohman
- , Igor L. Leskov
- & Brant E. Isakson
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Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and the platelet receptors GPIb and PAR4
Thrombin is a key proinflammatory protease regulating leukocyte trafficking at sites of vascular injury. Here the authors show that balanced thrombin interactions with platelet proteins PAR4, GPIbα and fibrin plays a major role in regulating this process.
- Zane S. Kaplan
- , Alessandro Zarpellon
- & Shaun P. Jackson
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Article
| Open AccessExposure to a youthful circulation rejuvenates bone repair through modulation of β-catenin
The reparative capacity of tissues decreases with age. Here, Baht et al. perform parabiosis experiments and provide evidence for the existence of a soluble factor produced by young, but not old, haematopoietic cells that is capable of improving fracture repair in old mice.
- Gurpreet S. Baht
- , David Silkstone
- & Benjamin A. Alman
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| Open AccessMicrobe-dependent lymphatic migration of neutrophils modulates lymphocyte proliferation in lymph nodes
Both sterile and microbial injuries lead to rapid neutrophil recruitment to the site of inflammation. Here the authors show that only neutrophils responding to microbial ligands leave inflamed skin and migrate to draining lymph nodes where they stimulate lymphocyte proliferation.
- Henry R. Hampton
- , Jacqueline Bailey
- & Tatyana Chtanova
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| Open AccessType I interferons regulate eomesodermin expression and the development of unconventional memory CD8+ T cells
Eomesodermin is the key transcription factor for the development of ‘virtual memory’ T cells that develop in the absence of antigen-driven activation. Here the authors show that type I interferons directly activate eomesodermin and contribute to the homeostasis of virtual memory CD8+T cells.
- Valérie Martinet
- , Sandrine Tonon
- & Stanislas Goriely
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| Open AccessExtracellular MRP8/14 is a regulator of β2 integrin-dependent neutrophil slow rolling and adhesion
MRP8/14 are actively secreted by myeloid cells during inflammation. Here the authors show that MRP8/14 play an important role in leukocyte recruitment to the inflammatory site, triggering an autocrine cascade that promotes neutrophil adhesion to the endothelium.
- Monika Pruenster
- , Angela R. M. Kurz
- & Markus Sperandio
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| Open AccessSphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin
The lipid sphingosine-1-phosphate (S1P) is known to mediate leukocyte recruitment in inflammation. Here, Nussbaum et al.show that S1P, via its receptor S1P3, also regulates leukocyte rolling on endothelium by promoting the presentation of the adhesion molecule P-selectin on the endothelial surface.
- Claudia Nussbaum
- , Sarah Bannenberg
- & Bodo Levkau
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| Open AccessMyeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarization
In response to microbial ligands, IRF5 promotes pro-inflammatory M1 macrophage activation and production of nitrous oxide. Here the authors show that nitrous oxide modifies IRF5 tyrosine residues as a negative feedback, limiting the inflammatory response and protecting from endotoxin shock.
- Geming Lu
- , Ruihua Zhang
- & Huabao Xiong
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Pre-B cell receptor binding to galectin-1 modifies galectin-1/carbohydrate affinity to modulate specific galectin-1/glycan lattice interactions
Galectin-1 (GAL1) is a secreted protein that binds to glycans and to the pre-B-cell receptor (pre-BCR). Here Bonzi et al. show that pre-BCR binding to GAL1 causes a conformational change in the GAL1 carbohydrate-binding site to inhibit binding to selected glycans.
- Jeremy Bonzi
- , Olivier Bornet
- & Latifa Elantak
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TH2 cells and their cytokines regulate formation and function of lymphatic vessels
Lymphatic vessels remodel in response to inflammatory conditions and T-cell-secreted cytokines. Here, the authors show that T helper type 2 cells inhibit lymphangiogenesis by secreting IL-4 and IL-13, and that blockade of these cytokines can alleviate allergic asthma symptoms by improving the lymphatic function in mice.
- Kihyuk Shin
- , Raghu P. Kataru
- & Seung-Hyo Lee
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Annexin A8 controls leukocyte recruitment to activated endothelial cells via cell surface delivery of CD63
The leukocyte receptor P-selectin translocates from Weibel-Palade bodies to the plasma membrane of activated endothelial cells, and is stabilized by CD63. Pöter et al. show that annexin A8 is required for P-selectin-mediated adhesion by regulating the supply of CD63 to the Weibel-Palade bodies.
- Michaela Poeter
- , Ines Brandherm
- & Ursula Rescher
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| Open AccessUnidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells
Exosomes released from cells can transfer RNA to recipient cells. In this study, the authors demonstrate that microRNAs in exosomes from T cells can be transferred to antigen-presenting cells during immune synapsis, and that this can alter gene expression, suggesting a new form of cellular communication.
- María Mittelbrunn
- , Cristina Gutiérrez-Vázquez
- & Francisco Sánchez-Madrid