Go to JCI Insight
Jci spelled out white on transparent.20160208
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews...
    • Cellular senescence in human disease (Apr 2018)
    • Fibrosis (Jan 2018)
    • Glia and Neurodegeneration (Sep 2017)
    • Transplantation (Jun 2017)
    • Nuclear Receptors (Apr 2017)
    • Metabolism and Inflammation (Jan 2017)
    • Hypoxia and Inflammation (Oct 2016)
    • View all review series...
  • Collections
    • Recently published
    • Commentaries
    • Concise Communication
    • Editorials
    • Opinion
    • Scientific Show Stoppers
    • Top read articles
    • In-Press Preview
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

Jci only white

  • About
  • Editors
  • Consulting Editors
  • For authors
  • Current issue
  • Past issues
  • By specialty
  • Subscribe
  • Alerts
  • Advertise
  • Contact
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • Brief Reports
  • Technical Advances
  • Commentaries
  • Editorials
  • Hindsight
  • Review series
  • Reviews
  • The Attending Physician
  • First Author Perspectives
  • Scientific Show Stoppers
  • Top read articles
  • Concise Communication

Commentary

  • 1,273 Articles
  • 0 Posts
  • ←
  • 1
  • 2
  • 3
  • …
  • 127
  • 128
  • →
Alternative macrophages in atherosclerosis: not always protective!
Benoit Pourcet, Bart Staels
Benoit Pourcet, Bart Staels
Published February 19, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI120123.
View: Text | PDF

Alternative macrophages in atherosclerosis: not always protective!

  • Text
  • PDF
Abstract

Atherosclerosis is a chronic inflammatory disease of the vasculature that is initiated by cholesterol deposition into the arterial wall, which triggers the infiltration of immune and inflammatory cells, including monocytes and macrophages. As atherosclerotic plaques progress, localized hypoxia promotes compensatory angiogenesis from the vasa vasorum. Immature neovessels are prone to leakage, thus destabilizing the plaque and leading to intraplaque hemorrhage. Macrophages with different phenotypes, ranging from classical inflammatory subtypes to alternatively activated antiinflammatory macrophages, have been identified in atherosclerotic lesions. Antiinflammatory hemoglobin-scavenging CD163+ macrophages are present in neovessel- and hemorrhage-rich areas; however, the role of these macrophages in atherogenesis has been unclear. In this issue of the JCI, Guo, Akahori, and colleagues show that CD163+ macrophages promote angiogenesis, vessel permeability, and leucocyte infiltration in human and mouse atherosclerotic lesions through a mechanism involving hemoglobin:haptoglobin/CD163/HIF1α-mediated VEGF induction. This study thus identifies proatherogenic properties of CD163+ macrophages, which previously were thought to be beneficial.

Authors

Benoit Pourcet, Bart Staels

×

SCN5A: the greatest HITS collection
David S. Park, Glenn I. Fishman
David S. Park, Glenn I. Fishman
Published February 19, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI99927.
View: Text | PDF

SCN5A: the greatest HITS collection

  • Text
  • PDF
Abstract

Heart failure (HF) has been referred to as the cardiovascular epidemic of our time. Understanding the molecular determinants of HF disease progression and mortality risk is of utmost importance. In this issue of the JCI, Zhang et al. uncover an important link between clinical HF mortality risk and a common variant that regulates SCN5A expression through microRNA-dependent (miR-dependent)mechanisms. They also demonstrate that haploinsufficiency of SCN5A is associated with increased accumulation of reactive oxygen species (ROS) in a genetically engineered murine model. Their data suggest that even modest depression of SCN5A expression may promote pathologic cardiac remodeling and progression of HF.

Authors

David S. Park, Glenn I. Fishman

×

All plugged up — noninvasive mucus score to assess airway dysfunction in asthma
Steve N. Georas
Steve N. Georas
Published February 5, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI99726.
View: Text | PDF

All plugged up — noninvasive mucus score to assess airway dysfunction in asthma

  • Text
  • PDF
Abstract

Asthma is remarkably heterogeneous, and there are multiple underlying inflammatory pathways and structural airway abnormalities that lead to symptomatic disease. Consequently, a current challenge in the field is to precisely characterize different types of asthma, with the goal of developing personalized approaches to therapy. In the current issue of the JCI, Dunican et al. developed a noninvasive way to assess airway dysfunction in asthma by measuring mucus accumulation using multidetector computed tomography (MDCT) and found that mucus plugging of small airways was remarkably common in subjects with severe asthma. This work highlights the importance of noninvasive imaging approaches in defining specific asthma subsets and guiding targeted therapies.

Authors

Steve N. Georas

×

Claudin-18: unexpected regulator of lung alveolar epithelial cell proliferation
Darrell N. Kotton
Darrell N. Kotton
Published February 5, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI99799.
View: Text | PDF

Claudin-18: unexpected regulator of lung alveolar epithelial cell proliferation

  • Text
  • PDF
Abstract

Claudin 18 (CLDN18) is a tight junction protein that is highly expressed in the lung. While mice lacking CLDN18 exhibit the expected loss of epithelial integrity in the lung, these animals also have unexpectedly large lungs. In this issue of the JCI, Zhou, Flodby, and colleagues reveal that the increased lung size of Cldn18–/– mice is the result of increased type 2 alveolar epithelial (AT2) cell proliferation. This increase in proliferation was shown to be driven by translocation of the transcriptional regulator Yes-associated protein (YAP) to the nucleus and subsequent induction of proliferative pathways. CLDN18-deficent mice also had increased frequency of lung adenocarcinomas. Together, the results of this study advance our understanding of the mechanisms that likely regulate homeostasis of the normal lung as well as promote the proliferative state of malignant cells found in lung adenocarcinomas thought to originate from AT2 cells.

Authors

Darrell N. Kotton

×

Newly found arsons ignite the fire of gut GVHD
Defu Zeng
Defu Zeng
Published January 29, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI98685.
View: Text | PDF

Newly found arsons ignite the fire of gut GVHD

  • Text
  • PDF
Abstract

Acute graft-versus-host disease (GVHD) in the gut is common following hematopoetic cell transplantation (HCT) and is associated with high mortality. However, it remains unclear whether Th1 or Th17 CD4+ T cells can initiate acute gut GVHD. In this issue of the JCI, Ullrich and colleagues identified a subset of CD4+ T cells that express high levels of IL-7Rα and granulocyte-macrophage CSF (IL-7RαhiGM-CSF+) cells that are involved in the induction of acute gut GVHD in murine models. The IL-7RαhiGM-CSF+ effector memory cells were BATF dependent, RORγt independent, produced large amounts of GM-CSF and IFN-γ, and released little IL-17. CD4+IL-7RαhiGM-CSF+ cells were not classical Th17 cells but had more of a Th1-like phenotype, despite their dependence on BATF. This work suggests that targeting the IL-7R/BATF/GM-CSF axis has therapeutic potential for treating acute gut GVHD.

Authors

Defu Zeng

×

Hypothalamic loss of Snord116 and Prader-Willi syndrome hyperphagia: the buck stops here?
Juan A. Rodriguez, Jeffrey M. Zigman
Juan A. Rodriguez, Jeffrey M. Zigman
Published January 29, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI99725.
View: Text | PDF

Hypothalamic loss of Snord116 and Prader-Willi syndrome hyperphagia: the buck stops here?

  • Text
  • PDF
Abstract

Hyperphagia and obesity are the best-known manifestations of Prader-Willi syndrome (PWS) and are responsible for most of the overall morbidity and mortality associated with the disease. Yet these PWS symptoms remain poorly understood and without effective pharmacologic therapies. Mouse models attempting to recapitulate both the genetic alterations and marked hyperphagia plus obesity of PWS have been enigmatic, leading to skepticism about the use of mouse models to investigate PWS. In this issue of the JCI, Polex-Wolf and colleagues challenge the skeptics by successfully inducing hyperphagia following bilateral mediobasal hypothalamic deletion of the Snord116 gene from adult mice. Obesity also resulted, although only in a subset of mice. While this approach represents an exciting advance, highlighting a pathologic effect of loss of mediobasal hypothalamic Snord116 expression on the development of PWS’s hallmark symptoms, the variability in the body-weight and body composition responses to this site-selective gene deletion raises several questions.

Authors

Juan A. Rodriguez, Jeffrey M. Zigman

×

A double negative: inhibition of hepatic Gi signaling improves glucose homeostasis
Allen M. Spiegel
Allen M. Spiegel
Published January 16, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI99037.
View: Text | PDF

A double negative: inhibition of hepatic Gi signaling improves glucose homeostasis

  • Text
  • PDF
Abstract

Hepatic glucose production (HGP) is a key determinant of glucose homeostasis. Glucagon binding to its cognate seven-transmembrane Gs-coupled receptor in hepatocytes stimulates cAMP production, resulting in increased HGP. In this issue of the JCI, Rossi and colleagues tested the hypothesis that activation of hepatic Gi–coupled receptors, which should inhibit cAMP production, would oppose the cAMP-inducing action of glucagon and thereby decrease HGP. Surprisingly, however, the opposite occurred: activation of Gi signaling increased HGP via a novel mechanism, while inhibition of Gi signaling reduced HGP. These results define a new physiologic role for hepatic Gi signaling and identify a potential therapeutic target for HGP regulation.

Authors

Allen M. Spiegel

×

The host protecting the tumor from the host — targeting PD‑L1 expressed by host cells
David H. Munn
David H. Munn
Published January 16, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI99047.
View: Text | PDF

The host protecting the tumor from the host — targeting PD‑L1 expressed by host cells

  • Text
  • PDF
Abstract

Tumors frequently escape from immune surveillance by hijacking the natural control mechanisms that regulate normal immune responses. The programmed death-1 receptor (PD‑1) on T cells normally helps limit excessive immune activation, but it can also suppress beneficial antitumor immunity. In the clinic, blocking either PD‑1 or one of its principal counterligands, programmed death–ligand 1 (PD‑L1), can lead to dramatic responses in certain patients. Because PD‑L1 can be expressed by both the tumor cells themselves and also the host cells, including host immune cells, the actual mechanistic target of therapy has remained unclear. In the current issue of the JCI, two papers, one by Tang and colleagues and the other by Lin and colleagues, used a variety of mouse tumor models to demonstrate that the relevant target for therapy in each case was the PD‑L1 molecules expressed by host cells and not by tumor cells. If this finding is generalized to humans, then it would suggest that the tumor persuades the host to actively suppress its own attempted immune response against the tumor cells.

Authors

David H. Munn

×

Unravelling the fate of functional PD1+ T cells in chronic viral hepatitis
Eleanor Barnes
Eleanor Barnes
Published January 8, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI99035.
View: Text | PDF

Unravelling the fate of functional PD1+ T cells in chronic viral hepatitis

  • Text
  • PDF
Abstract

Hepatitis B virus (HBV) infection can be managed clinically with nucleos(t)ide therapy, which suppresses viral replication; however, these drugs must often be used long term, as they are unable to fully eliminate the virus. For many patients, discontinuation of treatment results in viral resurgence and hepatic flare, and there is not a reliable way to identify those individuals that can be successfully taken off nucleos(t)ide therapy. In this issue of the JCI, Rivino and colleagues report on their use of a multipronged approach to investigate potential biomarkers indicative of HBV-infected patients who can safely stop nucleos(t)ide therapy. The authors identified a population of HBV-specific, PD1-positive T cells that was present in HBV-infected patients who successfully discontinued treatment without hepatic flare, but not in those that developed flare upon treatment cessation. Together, these results support the concept that PD1+ cells may play an important role in viral control, the further evaluation of this T cell subset in preventing hepatic flare, and the development of assays to better detect this PD1+ T cell population in HBV-infected patients on nucleos(t)ide therapy.

Authors

Eleanor Barnes

×

B cells as biomarkers: predicting immune checkpoint therapy adverse events
Shannon M. Liudahl, Lisa M. Coussens
Shannon M. Liudahl, Lisa M. Coussens
Published January 8, 2018
Citation Information: J Clin Invest. 2018. https://doi.org/10.1172/JCI99036.
View: Text | PDF

B cells as biomarkers: predicting immune checkpoint therapy adverse events

  • Text
  • PDF
Abstract

Immune checkpoint inhibitors are becoming a cornerstone of cancer immunotherapy as a result of their clinical success in relieving immune suppression and driving durable antitumor T cell responses in certain subsets of patients. Unfortunately, checkpoint inhibition is also associated with treatment-related toxicities that result in a myriad of side effects, ranging from mild and manageable to severe and debilitating. In this issue of the JCI, Das and colleagues report an association between early therapy-induced changes in circulating B cells and an increased risk of high-grade immune-related adverse events (IRAEs) in patients treated with checkpoint inhibitors that target cytotoxic T lymphocyte–associated antigen-4 (CTLA4) and programmed cell death protein 1 (PD1). These findings identify potential predictive biomarkers for high-grade IRAEs that may be leveraged to improve patient monitoring and may prompt new treatment strategies to prevent IRAEs.

Authors

Shannon M. Liudahl, Lisa M. Coussens

×
  • ←
  • 1
  • 2
  • 3
  • …
  • 127
  • 128
  • →

No posts were found with this tag.

Advertisement
Follow JCI: Facebook logo white Twitter logo v2 Rss icon
Copyright © 2018 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts