JCI insight

Immune cell profiling from pleural fluid offers prognostic value & potential targets in lung cancer: doi.org/10.1172/jci.... The Cover: Khatri et al. report macrophage reprogramming is associated with poor survival outcomes in lung cancer with metastasis to the pleural space.

A promising approach to overcome OXPHOS-dependent resistance in AML: doi.org/10.1172/jci.... @gouthamnarla.bsky.social & team report on a PP2A-B56α-based strategy that overcomes treatment resistance in preclinical AML models by targeting cell metabolism. @the-asci.org

I am so thrilled to share our years-long effort to understand the role of lymph node stromal cells in Castleman Disease! One of the biggest repositories of human lymph node stromal cell data. insight.jci.org/articles/vie...

What if Mycobacterium tuberculosis couldn’t evade macrophage defenses? doi.org/10.1172/jci.... @michaelshiloh.bsky.social & team identify SMURF2 as a conserved negative regulator of selective autophagy that suppresses macrophage control of M. tuberculosis.

🚨New paper alert!! Out in @insight.jci.org - highlights defects in Vdelta2 T cells in people living with obesity. Importantly we can see bariatric surgery restores these cells!! Led by @ciara.l.flynn but it takes a village. Thanks to funding from HRB. Find it here doi.org/10.1172/jci....

💫 A new axis that can fine-tune the immune response to glomerular & tubule cell damage: Chen et al. identify a myeloid cell-endothelial cell immunoregulatory axis whereby myeloid IL-1R1 activity constrained endothelial type I IFN generation to limit autoimmune kidney damage: doi.org/10.1172/jci....

This study links faulty DNA repair to abnormal immune responses: doi.org/10.1172/jci.... Yusuke Yamashita & team discover a partial defect in DNA repair weakens immune defenses yet promotes severe intestinal inflammation in mice.

Why does tuberculosis infection worsen HIV-1 outcomes? doi.org/10.1172/jci.... Cronin et al. demonstrate that the TB-altered immune microenvironment enriches the presence of genetically intact virus and impairs CD8 T cell-mediated antiviral responses.

An unexpected regulatory relationship reveals a therapeutic vulnerability in high-Wnt tumors: doi.org/10.1172/jci.... Using pancreatic cancer models, David M. Virshup, Babita Madan & team find that EPHA2 cooperates with Wnt in the tumor environment to inhibit MAPK signaling.

Unraveling links between prediabetes, cardiovascular disease, and hepatic steatosis. doi.org/10.1172/jci.... & team show how fatty liver may disrupt immune cells that clear harmful blood fats, which in turn increase heart disease risk.

Saturday Spotlight💫: Cenatus et al. describe a novel role for SMOC2 in promoting partial epithelial-to-mesenchymal transition and maladaptive repair mechanisms in renal tubular epithelial cells: doi.org/10.1172/jci.... @fondsrechercheqc.bsky.social

Presenting a novel axis that can fine-tune the immune response to glomerular and tubule cell damage: Chen et al. identify a myeloid cell-endothelial cell immunoregulatory axis whereby myeloid IL-1R1 activity constrained endothelial type I IFN generation to limit autoimmune kidney damage.

Mitochondrial gene therapy restores vision in a mouse model: doi.org/10.1172/jci.... Ai et al. report allotopic expression of mitochondrial ND6 restored retinal and optic nerve function and improved vision in a mouse model of mitochondrial disease.

Providing practical insights to support the next generation of physician-scientists: doi.org/10.1172/jci.... Thomas et al. used publicly available data and a survey to identify barriers and challenges experienced during grant writing for dual-degree trainees across the nation.

Can AI help identify the most aggressive variant subtypes of prostate cancer? Chen et al. report deep-learning based tools can provide quantitative assessment of molecular phenotypes in metastatic prostate cancer biopsies: doi.org/10.1172/jci.... @mishabeltran.bsky.social

Highlighting vacuolar H+-ATPase as a promising therapeutic target in Alzheimer’s disease: doi.org/10.1172/jci.... Using human tissue, primary neuronal cultures, and mouse models, Chen et al. reveal defective synaptic vesicle acidification impairs neurotransmission in AD.

Fantastic to not only see the final version of the paper published but also have it featured on the cover of the October issue of @insight.jci.org 🎉🎉🎉 #endothelialcells #liver #fibrosis

Mapping a path for predicting liver disease at earlier stages than current tests: doi.org/10.1172/jci.... @neildufton.bsky.social & team @qmulwhri.bsky.social mapped blood vessel changes during fibrosis & identified markers that could help predict early-stage liver disease. @timkendall.bsky.social

Cenatus et al. describe a novel role for SMOC2 in promoting partial epithelial-to-mesenchymal transition and maladaptive repair mechanisms in renal tubular epithelial cells: doi.org/10.1172/jci.... @fondsrechercheqc.bsky.social

The monoclonal antibody VYD2311 is in clinical trials for preventing COVID-19. In this Research Letter, @ianmellis.bsky.social et al. report that a laboratory-synthesized version of it inhibits many SARS-CoV-2 variants in laboratory-based infection models: doi.org/10.1172/jci....

A finding in mice suggests a new target for severe COVID-19: doi.org/10.1172/jci.... Eltobgy et al. discover that blocking the inflammatory protein caspase-11 restores virus-fighting T cells and improves viral clearance in mice.

Weekend read💫 : Immune cells ring the alarm! doi.org/10.1172/jci.... Hongji Zhang use a multiomic approach to investigate the drivers of surgical stress in the liver. They identify a neutrophil-Kupffer cell communication axis with potential for reducing inflammation and liver damage.

Therapeutic approaches for polycystic kidney disease (PKD) have largely been focused on eliminating cysts. Remadevi et al. demonstrate that fibrosis is a promising therapeutic target for PKD that can reduce kidney scarring and preserve kidney function. doi.org/10.1172/jci....

Immune cells ring the alarm! doi.org/10.1172/jci.... Zhang et al. use a multiomic approach to reveal how immune cells communicate to other hepatic cells after liver surgery and identify a potential target to reduce inflammation and liver damage.

The immediate effects of vaping have long-term consequences 🚬 doi.org/10.1172/jci.... Irina Petrache & team show that short-term e-cigarette use damages lung cells, impairs repair, and weakens antiviral defenses, raising concerns about long-term health risks.

Nice piece of work. We are proud to have contributed our expertise to this publication: JCI Insight - IFN-γ–producing self-reactive CD4+ T cells induce autoimmune adrenalitis in a mouse model of Addison’s disease insight.jci.org/articles/vie...

New from #NephFaculty Dr Ortiz-Melo and Dr Coffman in JCI Insight Proximal tubule ACE2 mediates early responses to hypertension by regulating intrarenal RAS and sodium homeostasis https://insight.jci.org/articles/view/179960

Blood-clotting complications in pediatric pneumonia infection can be life threatening. Huang et al. discover neutrophils promote thrombosis in pneumonia caused by Mycoplasma pneumoniae via NET-mediated endothelial activation involving TLR2 and JAK–STAT3 signaling: doi.org/10.1172/jci....

ICYMI💫: The GI symptoms that impair quality of life in childhood neurodegenerative disorders may be because bowel enteric neurons are also affected. In this Research Letter, Ziółkowska et al. characterize enteric pathology in MPSIIIA mice: doi.org/10.1172/jci.... @pattidickson.bsky.social

This Week in Research💫: Combination treatment offers a promising therapeutic approach for prostate tumors exhibiting lineage plasticity. Storck et al. report combined BET bromodomain & DNMT inhibition targets critical survival pathways in transdifferentiated prostate cancer: doi.org/10.1172/jci....