Towards the development of safer gene therapies for monogenic disease: doi.org/10.1172/jci.... David-Alexandre Gross & team @inserm.fr find an adaptive immune response can develop as early as a day after AAV gene therapy & is influenced by how the therapeutic gene is regulated, in mice.

Why do people with HIV have varied health risks for HIV-associated conditions despite effective antiretroviral therapy? doi.org/10.1172/jci.... Wang et al. report PWH whose virus is well controlled by treatment have different reservoir patterns that are linked to inflammation.

A new @insight.jci.org study from @pitt-immunology.bsky.social & @pittdeptofmed.bsky.social researchers sheds light on molecular pathways that distinguish severe and milder asthma & points to new therapeutic targets. Read more: www.immunology.pitt.edu/news/machine...

Hanako O. Ikeda & team explored iPSCs from patients with an inherited macular degeneration disorder, finding lysosomal dysfunction disrupts intracellular digestion & leads to drusen-like deposit accumulation, ECM degeneration, & cell death: doi.org/10.1172/jci....

Presenting the most comprehensive proteomic map of systemic lupus erythematosus to date! doi.org/10.1172/jci.... Leung et al. @imperialcollegeldn.bsky.social report potential therapeutic targets, biomarkers & autoantibody-linked proteomic signatures in SLE, providing a basis for precision medicine

For the renal scientific community: doi.org/10.1172/jci.... Rajasree Menon & team find reference tissue type, procurement method, and donor age and sex can substantially influence comparison between disease and reference samples. @miktmc.bsky.social @kpmproject.bsky.social

Sunday Spotlight: Challenging the view that complement activity promotes coronary arteritis in Kawasaki disease: doi.org/10.1172/jci.... Atici et al. identify the complement C3–C5 axis as a protective pathway in mouse KD that limits disease severity by facilitating clearance of microbial triggers

A highlight💫 from earlier this week: Exciting possibilities for immunotherapy in HIV: doi.org/10.1172/jci.... Sun et al. @ox.ac.uk used a high-affinity modified HIV-1 peptide to prime HLA-E restricted T cells, inhibiting HIV-1 replication in vitro.

Perm1 has many cytoprotective and organ protective functions: doi.org/10.1172/jci.... Here, Sadoshima & team discover Perm1 reduces harmful stress and limits cardiac damage in mouse models of heart attack by enhancing Nrf2-driven antioxidant defense. @the-asci.org #Cardioprotection

Challenging the view that complement activity promotes coronary arteritis in Kawasaki disease: doi.org/10.1172/jci.... Atici et al. identify the complement C3–C5 axis as a protective pathway in mouse KD that limits disease severity by facilitating clearance of microbial triggers

Asparagine depletion is a mainstay of treatment for ALL, yet leukemia cells often develop resistance doi.org/10.1172/jci.... Claude et al. find a strategy that prevents leukemia cells from producing their own amino acid—the treatment synergized with standard chemoagents in vivo

Exciting possibilities for immunotherapy in HIV: doi.org/10.1172/jci.... Sun et al. @ox.ac.uk used a high-affinity modified HIV-1 peptide to prime HLA-E restricted T cells, inhibiting HIV-1 replication in vitro.

Proposing a diagnostic shift for the monogenic autoimmune disorder APECED: doi.org/10.1172/jci.... Lionakis & team find APECED is recognized earlier by expanding the diagnostic criteria to include 3 early manifestations—APECED rash, autoimmune enteritis & enamel hypoplasia.

After stroke, does blocking NCX protect from or promote neurodegeneration? doi.org/10.1172/jci.... @gaborpetzold.bsky.social & team @dzne.science find NCX has harmful effects in neurons but is protective in astrocytes, influencing damaging brain activity & recovery in exp stroke

Saturday Spotlight💫: Cancers often arise in an environment characterized by fibrosis and inflammation Romain Desert et al. contribute a Review to JCI Insight’s 📗Special Issue on Fibrosis: The ECM in cancer-associated fibrosis: molecular mechanisms and clinical relevance: doi.org/10.1172/jci....

Presenting a new AI-based tool for measuring vascular tortuosity: doi.org/10.1172/jci.... Eric Nudleman & team used the tool to analyze mouse models of ischemic retinal disease, demonstrating that vascular tortuosity peaks with disease but persists long after recovery.

Might we restore human β cell function in T2D by blocking SASP? doi.org/10.1172/jci.... Iwasaki et al. discover a subset of senescent pancreatic β-cells that impair islet function by inducing secondary senescence in T2D, finding JAK inhibition restored β-cell function in models.

This aging-related communication axis helps explain why older age increases MASLD incidence: doi.org/10.1172/jci.... Diehl & team @dukemedschool.bsky.social describe an inter-organ aging axis in which hepatocytes determine the rate of organ aging during metabolic stress in mice.

This issue’s cover features work by Hua Jin & team on the discovery of a GZMK-expressing CD8+ T cell subset linked to severe intestinal GVHD and poorer patient outcomes after stem cell transplantation: doi.org/10.1172/jci.... Image generated using ChatGPT.

Cancers often arise in an environment characterized by fibrosis and inflammation Romain Desert et al. contribute a Review to JCI Insight’s 📗Special Issue on Fibrosis: The ECM in cancer-associated fibrosis: molecular mechanisms and clinical relevance: doi.org/10.1172/jci....

Fontan associated liver disease can occur after open-heart surgery for children with a single functional heart ventricle doi.org/10.1172/jci.... Here, Lehrich et al. identify a population of metabolically exhausted hepatocytes unique to FALD with advanced fibrosis

ICYMI⭐️ William M. Oldham @willoldham.bsky.social & team discover scar-forming cells in pulmonary fibrosis rely on alanine as a metabolic building block and simultaneously blocking its synthesis & uptake suppresses fibrosis in lung tissue: doi.org/10.1172/jci.... with @edykimlab.bsky.social

Saturday Spotlight⭐️ 📗From our Special Issue on Fibrosis Robert Schwabe & colleagues provide a Review on the shared mechanisms of organ #fibrosis: doi.org/10.1172/jci.... @rkramann.bsky.social @the-asci.org

Presenting a rigorous multicohort translational study: doi.org/10.1172/jci.... Baldwin et al. @columbiamed.bsky.social report on a blood protein that identifies people with lasting lung scarring after COVID19 & reveal ongoing airway cell changes that may drive fibrosis years after infection.

William M. Oldham @willoldham.bsky.social & team discover scar-forming cells in pulmonary fibrosis rely on alanine as a metabolic building block and simultaneously blocking its synthesis & uptake suppresses fibrosis in lung tissue: doi.org/10.1172/jci.... with @edykimlab.bsky.social

When wound healing gets stuck Chiara Francavilla & team identify a molecular signal in non-healing wounds that links dermokine with cell-cell adhesion: doi.org/10.1172/jci....

Primary sclerosing cholangitis is a progressive liver disease marked by periductal pathology doi.org/10.1172/jci.... Yunguan Wang & team find a communication axis involving stellate cells & macrophages around bile ducts implicated in driving liver fibrosis in pediatric patients

📗A Review from our Special Issue on Fibrosis: doi.org/10.1172/jci.... The inflammatory/fibrotic axis across organs: myelofibrosis as a model of reversibility by Greven et al.

📗From our Special Issue on Fibrosis Robert Schwabe & colleagues provide a Review on the shared mechanisms of organ #fibrosis: doi.org/10.1172/jci.... @the-asci.org

Spotlight: 📗From our Special Issue on Fibrosis Benjamin D. Humphreys @humphreyslab.bsky.social provide a Review on the shared mechanisms of organ #fibrosis: doi.org/10.1172/jci.... @the-asci.org