Journal of Clinical Investigation

IFN-λ fine tunes protective immunity during mucosal viral infection: doi.org/10.1172/JCI2... Associate Editor Pablo Penaloza-MacMaster @pemac.bsky.social provides an Editor’s Note on Feng et al.: doi.org/10.1172/JCI1...

Armoring #CARTcelltherapy with anti-inflammatory molecules offers new avenues for anti-fibrotic therapies in #ChronicKidneyDisease & other #Fibrosis conditions www.jci.org/articles/vie... @JonEpsteinLab #CellTherapy #CARTCell #TranslationalScience

IFN-λ boosts antiviral immunity while limiting inflammation: doi.org/10.1172/JCI1... Feng et al. report that IFN-λ treatment protected against hyperinflammation-driven tissue damage and enhanced viral clearance in a mouse model of genital HSV-2 infection.

XY0206: A promising sunitinib-derived FLT3 Inhibitor targeting therapy-resistant acute myeloid leukemia: doi.org/10.1172/JCI2... Associate editor Yiping Yang discusses the clinical relevance for XY0206 in an Editor’s Note on Shen et al.: doi.org/10.1172/JCI2... @the-asci.org

XY0206 exerts antileukemic activity even against treatment-insensitive acute myeloid leukemia doi.org/10.1172/JCI2... Shen et al. show that the sunitinib derivative was highly effective in models of FLT3-dependent resistance and patients with relapsed or refractory AML.

Sunday Read💫: A new role for Neuropeptide Y in cardiac electrophysiology. Olujimi A. Ajijola & team show Neuropeptide Y deficiency perturbs L-type calcium and outward potassium currents leading to ventricular arrhythmogenesis in mice 🧪: doi.org/10.1172/JCI2...

Saturday Highlight💫: Chemotherapy can prematurely age heart cells in children with cancer: doi.org/10.1172/JCI2... Turaga et al. discover upregulation of key senescence-associated genes indicating cellular aging throughout the hearts of children with treatment-related heart failure.

Good vibes keep worries at bay: a prefrontal-hypothalamic pathway engages positive affect to mitigate fear: doi.org/10.1172/JCI2... Quan-Son Le & Luis Rosas-Vidal provide a Commentary on Lin et al.: doi.org/10.1172/JCI2...

How can T cells limit brain bleeding after stroke? doi.org/10.1172/JCI2... Lu et al. explored immune cell responses in a mouse model of ischemic stroke, reporting that CD8 regulatory T cells protect against brain bleeding by shortening neutrophil lifespan.

Sepsis as a disease of endothelial dysfunction: doi.org/10.1172/JCI2... In this Review, Qin et al. present a framework to understand sepsis as a continuum of vascular manifestations, from endothelial activation to progressive endothelial dysfunction.

Mice missing 2 chromatin-regulating enzymes in developing face & heart cells show cleft palate & heart defects, mirroring Kleefstra syndrome: @dianavoss.bsky.social @jonepstein1.bsky.social & team find loss of GLP & G9a disrupts neural crest cell fate determination 🧪: doi.org/10.1172/JCI2...

🚨 🚨 NEW 🚨 🚨 "Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging" from Steven Finkbeiner and his team. Published in @jci.org

Our recently published study in @jci.org identifies nuclear PHB1 loss as a driver of alcohol-associated liver disease and colorectal liver metastasis. Blocking PHB1 nuclear export reduced liver injury, inflammation, oncogenic signaling, and metastasis. doi.org/10.1172/jci2...

As part of JCI’s review series on emerging therapeutic strategies in breast cancer, Seriak et al. present: Next-generation CDK inhibitors in hormone receptor-positive/HER2-negative breast cancer: doi.org/10.1172/JCI2...

@matthewoser.bsky.social & team identify the polycomb scaffolding subunit EED as a protein that helps small cell lung cancer keep its neuroendocrine state by repressing lung adenocarcinoma genes: doi.org/10.1172/JCI1... @the-asci.org

Chemotherapy drugs can prematurely age heart cells in children with cancer: doi.org/10.1172/JCI2... Turaga et al. discover upregulation of key senescence-associated genes indicating cellular aging throughout the hearts of children with treatment-related heart failure.

As part of JCI’s review series on emerging therapeutic strategies in breast cancer, Kristen S. Young & Sean W. Fanning present: Selective estrogen receptor degraders and their impact on the breast cancer immune microenvironment: doi.org/10.1172/JCI2...

Commentary: Cells heal themselves: gene edited hematopoietic stem cells restore frataxin deficiency in multiple organs: doi.org/10.1172/JCI2... Lucy R. Osborne discusses Sivakumar et al.: doi.org/10.1172/JCI2...

We did a thing and it got published. More than 5 years of work. More about monocytes and ALI in our future. @jci.org #NIH, #NHLBI, #sepsissurvival

A study in @jci.org led by @danafarber.bsky.social’s @sethilab.bsky.social on therapy-associated polyposis - which can develop decades after cancer treatment - identified lasting molecular evidence of genetic damage linked to chemotherapy in precancerous colorectal growths. ➡️bit.ly/4hIrB70

Many underlying factors contributing to immunotherapy resistance remain unclear. Now published in the Oct 15 issue of JCI, we demonstrate that tumors amplified for NLRP3 drive the suppression of MHC class I antigen presentation and immune evasion. www.jci.org/articles/vie... @jci.org #NLRP3

Modeling neurodegeneration in human cells: doi.org/10.1172/JCI2... In this Review, Wang et al. describe the potential of human cell-based models to reveal disease mechanisms and serve as platforms for drug discovery.

Sunday Feature💫: @hellmutaugustin.bsky.social & team @uniheidelberg.bsky.social find ectodomain cleavage of the vascular receptor Tie1 distinguishes the inflammatory from the angiogenic functions of Angiopoietin-Tie signaling, uncoupling two fundamental vascular programs: doi.org/10.1172/JCI2...

Resolving the links between efferocytosis and DNMT3A mutation-driven clonal hematopoiesis in atherosclerosis: doi.org/10.1172/JCI2... Aarti Asnani comments on Avrampou et al.: doi.org/10.1172/JCI2...

As part of JCI’s review series on emerging therapeutic strategies in breast cancer, Arteaga & colleagues present: PI3K signaling in breast cancer: therapeutic advances versus adaptive resistance: doi.org/10.1172/JCI2... @the-asci.org

This Research Letter reports a new role for Neuropeptide Y in cardiac electrophysiology Olujimi A. Ajijola & team show Neuropeptide Y deficiency perturbs L-type calcium and outward potassium currents leading to ventricular arrhythmogenesis in mice: doi.org/10.1172/JCI2...

Malignant peripheral nerve sheath tumors are rare, aggressive soft tissue sarcomas. Hirbe & team show dual inhibition with FAK and RAF/MEK in mice overcomes resistance, suppresses growth, and induces tumor regression in chromosome 8 gain MPNST: doi.org/10.1172/JCI2... @sargoshoe.bsky.social

In this Research Letter, Nilay S. Sethi & team find chemotherapy leaves lasting DNA scars in precancerous colon polyps decades after treatment, helping explain the rare, late complication in childhood cancer survivors, therapy-associated polyposis: doi.org/10.1172/JCI2...

Blocking EFHD1 protects against liver damage in MASH models: doi.org/10.1172/JCI2... @dipayan.bsky.social & team identify EFHD1 as a protein in liver cells that triggers a maladaptive viral response during metabolic stress. EFHD1 loss in mouse liver resulted in spaghetti-like mitochondria.

@hellmutaugustin.bsky.social & team @uniheidelberg.bsky.social find ectodomain cleavage of the vascular receptor Tie1 distinguishes the inflammatory from the angiogenic functions of Angiopoietin-Tie signaling, uncoupling two fundamental vascular programs: doi.org/10.1172/JCI2...

Sunday Read💫: What can 3,839,400 sibling pairs tell us about autoimmune disease? Eriksson et al. @ki.se quantified genetic correlations across 22 autoimmune diseases, showing substantial cluster-specific genetic overlap that largely aligns with affected tissue types: doi.org/10.1172/JCI2...

Weekend Spotlight💫: As part of JCI’s review series on emerging therapeutic strategies in breast cancer, Fanucci et al. present: Toward targeted therapeutics for lobular breast cancer: doi.org/10.1172/JCI2... stoverlab.bsky.social

A vasopressin gate transforms social distress into caregiving: doi.org/10.1172/JCI2... Jonathan P. Fadok comments on Geng et al.: doi.org/10.1172/JCI2...

Hypothalamic-amygdala-VTA circuit reinforces caregiving-like behavior doi.org/10.1172/JCI2... Geng et al. show that vasopressin secretion initiates a positive feedback loop to promote grooming of an injured mouse, transforming distress into a prosocial response.

As part of JCI’s review series on emerging therapeutic strategies in breast cancer, Kay et al. @petermaccc.bsky.social present: Breast cancer immunogenicity as a spectrum: evolving concepts and therapeutic implications: doi.org/10.1172/JCI2...