JCI insight最新文献

{"title":"Virome antigens as triggers for immune recognition of mutant clones in normal tissues.","authors":"Natalie E Andresen, Heehwa G Son, Joongho J Joh, Shadmehr Demehri","doi":"10.1172/jci.insight.203484","DOIUrl":"https://doi.org/10.1172/jci.insight.203484","url":null,"abstract":"","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of pulmonary IL-21 expression during latent TB and Mtb/SIV co-infection.","authors":"Vinay Shivanna, Renee D Escalona, Colin Chuba, Shashi Prakash Singh, Ahmed A Moustafa, J Quincy Brown, Chenyao Xiao, Sangkyu Kim, Edward J Dick, Smriti Mehra, Mirko Paiardini, Riti Sharan","doi":"10.1172/jci.insight.199217","DOIUrl":"https://doi.org/10.1172/jci.insight.199217","url":null,"abstract":"<p><p>TB (Tuberculosis) and HIV co-infection remains a major global health challenge, with limited understanding of how these pathogens impact local immune responses in the lungs. This study is the first to investigate the modulation of IL-21 during LTBI and Mycobacterium tuberculosis (Mtb)/ Simian Immunodeficiency Virus (SIV) co-infection in non-human primates (NHP). We show that IL-21 expression, predominantly derived from CD4⁺ T cells, is significantly reduced in lungs of Mtb/SIV co-infected macaques, especially in the absence of cART. Although cART and cART with 3HP partially restore IL-21-producing CD4⁺ T cells, levels remain below those in LTBI, indicating ongoing immune impairment. Spatial transcriptomic analysis suggests localized alterations in immune signaling, including differences in STAT1- and STAT3-associated transcriptional profiles and reduced Mtb-specific IFN-γ responses in co-infected animals. Together, our findings indicate that IL-21-producing CD4⁺ T cells are selectively and persistently impaired in the lungs during Mtb/SIV co-infection despite antimicrobial and antiviral therapy. These results highlight a compartment-specific deficit in immune reconstitution and suggest that IL-21-associated pathways may warrant further investigation as potential targets for host-directed therapeutic strategies.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TCF7L2 promotes abdominal aortic aneurysm through smooth muscle cell-mediated extracellular matrix remodeling.","authors":"Yongjie Deng, Yaozhong Liu, Yang Zhao, Hongyu Liu, Guizhen Zhao, Zhenguo Wang, Xu Zhang, Chao Xue, Wei Huang, Tianqing Zhu, Haocheng Lu, Yanhong Guo, Lin Chang, Ida Surakka, Y Eugene Chen, Jifeng Zhang","doi":"10.1172/jci.insight.195681","DOIUrl":"https://doi.org/10.1172/jci.insight.195681","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) lacks effective pharmacological therapies. Here, we investigate transcription factor 7-like 2 (TCF7L2), a genetic locus associated with both thoracic and abdominal aortic aneurysms, to elucidate its role in AAA pathogenesis. Integrating summary-data-based Mendelian randomization (SMR) with single-cell RNA sequencing (scRNA-seq) of human and mouse aortas, we identify TCF7L2 as a gene enriched in vascular smooth muscle cells (VSMCs) and causally linked to AAA development. Smooth muscle cell-specific TCF7L2 knockout significantly attenuates AAA formation across three distinct murine models (Ang II infusion-, BAPN/Ang II co-administration-, and elastase-induced AAA), independent of systemic blood pressure or lipid levels. Mechanistic studies reveal that TCF7L2 directly upregulates MMP14 and downregulates TIMP3 expression in vitro and in vivo, driving MMP2-mediated extracellular matrix (ECM) degradation. Concurrently, TCF7L2 represses integrin β1 (ITGB1) expression, reducing VSMC adhesion to the ECM. Collectively, these findings identify TCF7L2 as a key driver of pathological vascular remodeling in AAA, suggesting that targeting TCF7L2 may offer a novel therapeutic strategy for limiting AAA progression.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PD-1-targeted IL-15 mutein activates CD8+ and CD4+ T cells in infection and cancer.","authors":"Isaraphorn Pratumchai, Marie Bernardo, Julien Tessier, Jaroslav Zak, Kristi L Marquardt, Joon Sang Lee, Maheeka Bimal, AHyun Choi, Anthony M Byers, Mikielia G Devonish, Roberto Carrio, Dan Lu, Stella A Martomo, Jeegar Patel, Yu-An Zhang, Ingeborg M Langohr, Virna Cortez-Retamozo, Dinesh S Bangari, Angela Hadjipanayis, Xiangming Li, Valeria R Fantin, Donald R Shaffer, John R Teijaro","doi":"10.1172/jci.insight.198701","DOIUrl":"https://doi.org/10.1172/jci.insight.198701","url":null,"abstract":"<p><p>Immune checkpoint inhibitors have transformed cancer therapy, yet many patients fail to achieve durable responses due to insufficient T cell reinvigoration. Cytokines offer promise for enhancing immunotherapy, but their clinical use is limited by toxicity and a narrow therapeutic index. Immunocytokines, engineered fusion proteins combining antibody specificity with cytokine activity, aim to overcome these challenges by targeting cytokine delivery to immune cells or the tumor microenvironment. We describe SAR445877 (SAR'877), a novel PD-1-targeted immunocytokine that fuses a high-affinity anti-PD-1 antibody with a detuned IL-15/IL-15Rα sushi domain complex. SAR'877 blocks PD-1/PD-L1 and PD-1/PD-L2 interactions while selectively delivering IL-15 signals to PD-1+ T cells, enhancing proliferation and activation of antigen-experienced CD8+ and CD4+ T cells and NK cells, while minimizing systemic inflammation. Mechanistically, SAR'877 activates STAT5 signaling in PD-1+ lymphocytes and restores effector function in exhausted T cells. In preclinical models, a murine surrogate of SAR'877 accelerated viral clearance and induced robust anti-tumor immunity by expanding cytotoxic CD8+ T cells and promoting Th1 polarization. Notably, SAR'877 outperformed anti-PD-1 plus untargeted IL-15, highlighting the therapeutic potential of targeted IL-15 delivery. These findings position SAR'877 as a promising next-generation immunotherapy with enhanced efficacy and reduced cytokine-associated toxicities.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A platform for parallel T cell receptor cloning and testing enables anti-neoantigen tumor immunotherapy.","authors":"Alexander M Rowe, Smriti Chaurasia, Wenzhong Wei, Laura García-Diéguez, Katherine Querry, Johnathon G Schiebel, Christy Smolak, Alexander G Muralles, Daniel Wikenheiser, Kevin Quann, Collin Pirner, Kentin Codispot, Mark J Shlomchik, Warren D Shlomchik","doi":"10.1172/jci.insight.203622","DOIUrl":"https://doi.org/10.1172/jci.insight.203622","url":null,"abstract":"<p><p>Tumor-infiltrating CD8 cells recognize neoantigens created by tumor-specific mutations. Nonetheless, even after checkpoint inhibitor therapy, most patients progress. A deeper understanding of anti-tumor responses could facilitate development of better therapies. To enable such studies, we applied TCXpress, a high throughput platform that clones fully expressible TCRs from single cells into retro- or lenti- viral vectors without sequencing or gene synthesis, to study TCRs from CD8 cells infiltrating mouse MC38 tumors. We expressed cloned TCRs in reporter cells and interrogated TCR specificity by coculturing them with B6WT3 cells transduced with tandem minigenes encoding predicted neoantigens. We isolated TCRs reactive against epitopes from mutant Rpl18, Adpgk, Psmd2, and Zc3h7b along with self-reactive TCRs that recognized normal B6 and MC38 cells. Importantly, we successfully treated MC38-bearing mice with T cells transduced with anti-Rpl18 TCRs. These results establish a system that could be used to study many types of T cell responses and validates a therapeutic approach that could be tested in the clinic.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of distinct genomic landscapes in young-onset gBRCA1/2 breast cancer.","authors":"Mwangala P Akamandisa, Mingyi Xia, Wilson Cheah, Bradley Wubbenhorst, Kurt P D'Andrea, Mengyao Fan, Jake S Shilan, Dana Pueschl, Anupma Nayak, Hayley McKenzie, William Tapper, Ellen R Copson, Ramsey I Cutress, Susan M Domchek, Diana M Eccles, Katherine L Nathanson","doi":"10.1172/jci.insight.203005","DOIUrl":"https://doi.org/10.1172/jci.insight.203005","url":null,"abstract":"<p><p>Germline BRCA1/2 pathogenic variant (PV) carriers have elevated young-onset breast cancer risk. To define the pretreatment genomic landscapes of young-onset gBRCA-associated breast cancer, we evaluated 136 treatment-naïve tumors diagnosed before age 50 (92.6% ≤40): gBRCA1 86(63.2%); gBRCA2 50(36.8%) in the prospective POSH study, and 66 noncarriers from The Cancer Genome Atlas. Using whole exome sequencing, we analyzed somatic variation, allele-specific loss of heterozygosity (asLOH), homologous recombination deficiency (HRD), and single-base substitution signatures (SBS). gBRCA1(93%) and gBRCA2(96%) breast cancers had high rates of asLOH, but differed significantly in average HRD scores (57.4 ± 1.3 vs 43.7 ± 1.5, P < 0.0001) and median SBS composition (%): SBS1 (aging-associated) 12.9 vs 7.3, P = 0.013; SBS18 (reactive oxygen species [ROS]-associated) 1.4 vs 0, P = 0.007; and SBS3 (HRD-associated) 27.3 vs 42.6, P = 0.002. Compared to gBRCA2 tumors, gBRCA1 tumors with asLOH were significantly enriched for alterations in Hallmark ROS, DNA repair, and epithelial-mesenchymal transition pathways. In ER-positive, HER2-negative tumors from gBRCA1/2 carriers compared to noncarriers, we found significant enrichment of RB1 (OR:6.3;95%CI:2.8-15.4;padj = 0.001), TP53 (OR:4.6;95%CI:1.9-12.1;padj = 0.017), FAT1 (OR:3.9;95%CI:1.84-8.7;padj = 0.013), and MYC (OR:4.0;95%CI:1.8-9.1;padj = 0.017) SNV/indels/CNVs, associated with CDK4/6i resistance. Together, these findings demonstrate significant differences between gBRCA1 and gBRCA2-associated breast cancers, and preexisting CDK4/6i resistance mechanisms supporting prospective trials with individualized therapy for gBRCA1 vs gBRCA2 carriers, and comparing PARPi to CDK4/6i for ER-positive gBRCA1/2-associated breast cancer.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilizing and strengthening the U.S. physician-scientist faculty workforce in academic medicine: a proposed institutional framework.","authors":"Christopher S Williams, Megan Allen, Paige Cooper Byas, John B Hawley, Louis J Muglia, E Dale Abel, Julie A Bastarache, Carolyn S Calfee, John M Carethers, David N Cornfield, Oliver Eickelberg, Emily J Gallagher, Anna Greka, Peter J Gruber, Anthony N Hollenberg, Heidi H Kong, Barbara I Kazmierczak, Gary A Koretzky, Mark Lachs, Deborah J Lenschow, Geoffrey S Pitt, Don C Rockey, Lisa M Satlin, Barry P Sleckman, David A Stoltz, Jatin M Vyas, Thomas J Wang, Kyu Y Rhee","doi":"10.1172/jci.insight.205939","DOIUrl":"https://doi.org/10.1172/jci.insight.205939","url":null,"abstract":"<p><p>Physician-scientists represent one of the most impactful, yet underrecognized, innovations of 20th century academic medicine. Defined by a commitment to full-time careers in investigative work, physician-scientists have repeatedly demonstrated a unique ability to identify and solve problems of unmet medical need in a focused and intentional manner using their dual training in clinical medicine and the scientific method as both stethoscope and scalpel. Unfortunately, mounting financial pressures from both the clinical and research marketplaces have placed this storied workforce in jeopardy due to the absence of a dedicated and explicitly defined vocational structure and business model. This white paper reports the output of a consortium of academic medical centers, foundations and professional societies seeking to remedy this deficiency. This consortium specifically developed a framework to formalize the career path of physician-scientist faculty into a professionally unified and financially sustainable structure in a way that could be adopted to different U.S. academic medical centers and health systems. Key components of this framework included an administratively operational definition of physician-scientists, and three central and interconnected pillars (academic, financial, and organizational) that are rooted in this foundational definition. Herein, we detail core concepts and concrete recommendations.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bispecific targeting of CHI3L1 and PD-1 as a therapeutic strategy for pulmonary fibrosis.","authors":"Han-Seok Jeong, Takayuki Sadanaga, Joyce H Lee, Suchitra Kamle, Bing Ma, Yang Zhou, Sung Jae Shin, Jack A Elias, Chun Geun Lee","doi":"10.1172/jci.insight.201609","DOIUrl":"https://doi.org/10.1172/jci.insight.201609","url":null,"abstract":"<p><p>CHI3L1, a chitinase-like protein, is implicated in pulmonary fibrosis, yet its mechanisms incompletely understood. In this study, we demonstrated that CHI3L1 coordinates profibrotic macrophage activation and invasive myofibroblast differentiation, and their crosstalk. In vitro, CHI3L1 drove M2-like macrophage polarization as evidenced by increased CD163, CD206, and PD-L1, and amplified TGF-β1-induced fibroblast responses, including myofibroblast transformation, migration, and invasion. Mechanistically, CHI3L1 enhanced TGF-β1 signaling through SMAD, AKT, and ERK pathways, and PD-L1 was required for CHI3L1/TGF-β1-driven myofibroblast transformation. Co-culture studies further demonstrated the ability of CHI3L1 to induce profibrotic macrophage activation that enhanced myofibroblast transformation mediated via a CD44-PD-L1 axis. In vivo, following bleomycin challenge, CHI3L1 transgenic mice exhibited increased PD-L1+ M2 macrophages, PD-L1+/PDGFRα+ fibroblasts, and PD-1+ immune cells compared with wild-type controls. Therapeutically, combined anti-CHI3L1 and anti-PD-1 antibodies, as well as a bispecific anti-CHI3L1-anti-PD-1 antibody, produced greater anti-fibrotic efficacy than monotherapy. These findings demonstrate crosstalk between CHI3L1 and the PD-1/PD-L1 pathway that promotes profibrotic macrophage activation and invasive fibroblast differentiation and support dual targeting of CHI3L1 and PD-1/PD-L1 as a promising therapeutic strategy for pulmonary fibrosis.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A lipid-immune network signature defines susceptibility to asparaginase-associated pancreatitis.","authors":"Cheng-Yu Tsai, Na Bo, Thai Hoa Tran, Maisam Abu-El-Haija, Gayathri Swaminathan, Bomi Lee, Sudhir Ghandikota, Li Wen, Yves Théorêt, Steven D Mittelman, Elena J Ladas, Anil G Jegga, Lewis B Silverman, Ying Ding, Sohail Z Husain","doi":"10.1172/jci.insight.202662","DOIUrl":"https://doi.org/10.1172/jci.insight.202662","url":null,"abstract":"<p><strong>Background: </strong>Asparaginase is essential for curing acute lymphoblastic leukemia (ALL), but its use is limited by asparaginase-associated pancreatitis (AAP), a severe and unpredictable toxicity lacking validated prospective biomarkers. We sought to define early systemic molecular features of susceptibility to AAP.</p><p><strong>Methods: </strong>We performed longitudinal lipidomic and proteomic profiling in two independent pediatric ALL cohorts (n = 161; 79 AAP cases, 82 controls) using paired blood samples collected before asparaginase exposure and at the end of induction therapy (including a single dose of asparaginase), thereby capturing pre-injury biology rather than consequences of pancreatitis. We applied differential abundance and network-based analyses, and integrated lipid-cytokine associations using proteomics.</p><p><strong>Results: </strong>Across cohorts, we identified a reproducible lysophosphatidylcholine (LPC)-centered signature characterized by attenuated induction therapy-associated LPC responses and disruption of LPC co-regulation at the network level. Proteomic profiling revealed enrichment of cytokine signaling pathways, and integrative analyses demonstrated altered lipid-cytokine coupling, including a flip in association direction for LPC species and interleukin-18 (IL-18) between cases and controls. Although IL-18/LPC ratios do not differ globally, elevated post-induction IL-18/LPC ratios identify AAP risk within a protocol-defined very high-risk ALL subgroup (AUC = 0.81).</p><p><strong>Conclusion: </strong>These findings support a systems-level model in which failure of coordinated lipid-immune responses under therapeutic stress confers vulnerability to AAP, providing a framework for validation and mitigation strategies.</p><p><strong>Trial registration: </strong>NCT00400946; NCT01574274; NCT03020030 (parent trials).</p><p><strong>Funding: </strong>Servier Pharmaceuticals (IIT-95014-027-USA); SDRC (P30DK116074); Stanford SPARK; Fonds de Recherche du Québec - Santé; Fondation Charles-Bruneau; The Leukemia & Lymphoma Society of Canada.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NAD+ augmentation by nicotinamide riboside engages SLIT2/ROBO1 signaling to attenuate Th17 inflammation in psoriasis.","authors":"Kim Han, Rachael J Klein, Thomas C Recupero, Anna Chiara Russo, Rahul Sharma, Anand K Gupta, Shahin Hassanzadeh, Rebecca D Huffstutler, Pradeep K Dagur, Bryan Fisk, Neelam R Redekar, Michael N Sack","doi":"10.1172/jci.insight.203826","DOIUrl":"https://doi.org/10.1172/jci.insight.203826","url":null,"abstract":"<p><p>Enhancing NAD+ levels with nicotinamide riboside (NR) confers anti-inflammatory effects in human disease, although immunoregulatory mechanisms remain poorly characterized. We previously showed that ex vivo NR supplementation of primary CD4+ T cells from psoriatic individuals dampened immune responsiveness. To validate this in vivo, we performed a randomized, placebo-controlled NR supplementation study in individuals with mild-to-moderate psoriasis. Participants received oral NR (500 mg twice daily) or matching placebo for 4 weeks, with blood samples collected at baseline and after supplementation. NR reduced Th17 immune responsiveness. Bulk CD4+ T cell RNA-seq identified induction of the SLIT-ROBO signaling pathway. NR supplementation increased circulating SLIT2 levels and enhanced SLIT2 production in dermal fibroblasts. Pharmacologic and genetic interrogation in CD4+ T cells and fibroblasts demonstrated that SLIT2, acting through the ROBO1 receptor, inhibited Rho GTPase signaling, thereby attenuating canonical Th17 polarization and fibroblast inflammatory activation. These findings indicate that NAD+ augmentation exerts anti-inflammatory effects in psoriasis through SLIT2-ROBO1-mediated crosstalk between dermal fibroblasts and circulating CD4+ T cells, leading to suppression of Th17-driven inflammation.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":" ","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}