Journal of Immunology Research最新文献

{"title":"Integrating AI, RNA Vaccines, and CAR-T Cells for Personalized Treatment.","authors":"Diala Haykal, Brigitte Dréno","doi":"10.1155/jimr/2275385","DOIUrl":"10.1155/jimr/2275385","url":null,"abstract":"<p><p>Oncology is undergoing a profound transformation driven by the convergence of artificial intelligence (AI), RNA-based vaccines, and chimeric antigen receptor T-cell (CAR-T) therapies. Individually, these technologies have advanced cancer diagnosis, treatment, and patient stratification. AI-driven approaches enhance drug discovery, optimize clinical trial design, and enable personalized therapeutic decision-making. RNA vaccines provide a flexible platform for encoding tumor-specific neoantigens, while CAR-T therapies enable targeted immune-mediated tumor cell elimination. Early-phase clinical trials, particularly those combining RNA vaccines with immune checkpoint inhibitors, have demonstrated promising improvements in recurrence-free survival (RFS) and immunogenicity. However, evidence supporting direct combinations of RNA vaccines and CAR-T therapies remains largely preclinical or limited to early-phase investigation and should therefore be interpreted with caution. This review explores how AI facilitates neoantigen discovery, RNA vaccine optimization, and CAR-T cell engineering, and examines the emerging interplay between these modalities. While their integration represents a compelling framework for personalized oncology, significant challenges remain, including clinical validation, scalability, regulatory oversight, and equitable access.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e2275385"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Throughput Heterospheroid-Based Screening Identifies Drugs That Reprogram Tumor-Associated Macrophages.","authors":"Hiroyuki Tsuchiya, Takehiko Hanaki, Mayu Obora, Jun Yoshida, Mikiya Kishino, Yoshiyuki Fujiwara, Daisuke Nanba","doi":"10.1155/jimr/2889509","DOIUrl":"10.1155/jimr/2889509","url":null,"abstract":"<p><p>The tumor microenvironment (TME) provides a niche for immune evasion and immunotherapy resistance, in part, by recruiting pro-tumor M2-like macrophages. In the present study, using heterospheroids consisting of cancer cells and macrophages, we identified TAM activators, which are compounds that reprogram M2-like tumor-associated macrophages (TAMs) toward the antitumor M1-like phenotype. THP-1- or human peripheral monocyte-derived macrophages were co-cultured with liver cancer (LC) cells in an ultra-low attachment dish to generate heterospheroids. Cell surface marker expression and macrophage infiltration into the heterospheroids were assessed by flow cytometry and fluorescence microscopy, respectively. Lipopolysaccharide (LPS) and interferon-γ (IFNγ)-induced M1 marker expression was observed on the macrophages in the homospheroids; however, this induction was suppressed in heterospheroids. Microscopic imaging revealed that macrophage infiltration into the heterospheroids was decreased in the presence of LPS and IFNγ, which prompted us to develop a high-content imaging screen. We identified two compounds [alprostadil (prostaglandin E1) and HX531] with TAM-activating activity. RNA-seq analysis revealed that HX531 modulated the immune and IFN response in cancer cells and cell division in macrophages. Moreover, alprostadil promoted the M1-like polarization of TAMs, increased tumor-infiltrating CD8⁺ T cells, and enhanced anti-PD-1 antibody therapeutic efficacy in a syngeneic tumor-bearing mouse. In conclusion, the heterospheroid culture recapitulates the immunosuppressive TME, which prevents the M1 polarization of TAMs. It provides a new platform for screening TAM activators and will enable the development of novel cancer immunotherapeutics when combined with high-content imaging analysis.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e2889509"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot Study to Improve In Vitro Identification of Culprit Drugs in SJS/TEN Using Granzyme B and Granulysin Secretion Assays.","authors":"Yuttana Srinoulprasert, Somkiat Ud-Naen, Tunsuda Tansit, Papapit Tuchinda, Chamard Wongsa, Jettanong Klaewsongkram","doi":"10.1155/jimr/8497493","DOIUrl":"10.1155/jimr/8497493","url":null,"abstract":"<p><strong>Introduction: </strong>Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) are severe cutaneous adverse drug reactions (SCARs) with high morbidity and mortality. Accurate identification of the culprit drug is critical and remains challenging, whereas current in vitro tests such as lymphocyte transformation test (LTT) have limited sensitivity. To evaluate measuring granulysin (Gr) and granzyme B (GZB) secretion from drug-stimulated peripheral blood mononuclear cells (PBMCs) for identification of culprit drugs and to compare their diagnostic performance with conventional LTT.</p><p><strong>Materials and methods: </strong>PBMCs from 12 patients with confirmed SJS/TEN were incubated with suspected drugs. LTT and Gr/GZB detection assays were performed on day 3 and 6. Levels of Gr and GZB were quantified from supernatants, and results were normalized as production ratios. Cut-off values were defined using receiver operating characteristic (ROC) curve analysis with high specificity thresholds.</p><p><strong>Results: </strong>GZB detection on day 3 yielded the highest sensitivity (8/12) compared to LTT (6/12) and Gr detection. Combining GZB and Gr detection improved the positive rate to 10/12. ROC curve analysis demonstrated higher AUCs for cytokine assay than for LTT, particularly for GZB at day 3. Combining GZB and Gr detection with LTT did not significantly increase diagnostic yield.</p><p><strong>Conclusion: </strong>The detection of GZB and Gr production in PBMC cultures provided a more sensitive and specific method than the conventional LTT for identifying culprit drugs in SJS/TEN. In particular, GZB detection at day 3 provided a shorter assay duration, avoided radioactive labeling, and demonstrated superior diagnostic performance. This cytokine-based approach may represent a practical and safer alternative to enhance drug causality assessment in patients with SCARs.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e8497493"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chaiyin Granules Improve Acute Lung Injury by Regulating Gut Microbiota and Unsaturated Fatty Acid Mediated Wnt/β-Catenin Signaling Pathway.","authors":"Wenting Ni, He Xiao, Qun Feng, Shirong Li, Jingchun Yao, Guimin Zhang","doi":"10.1155/jimr/7225946","DOIUrl":"10.1155/jimr/7225946","url":null,"abstract":"<p><strong>Aim of study: </strong>This study aimed to investigate the efficacy and mechanism of Chaiyin granules (CY) in improving acute lung injury (ALI) based on the gut-lung axis.</p><p><strong>Materials and methods: </strong>UHPLC-ESI-Q-Exactive Orbitrap MS was used to analyze the active ingredients of CY. Establishment of lipopolysaccharide (LPS)-induced ALI mouse model and grouping: control, model, CYL (1.56 g/kg), CYM (3.12 g/kg), CYH (6.24 g/kg), and Dex (2 mg/kg) groups. The lung index and wet/dry (W/D) weight ratio of the lungs were calculated. The pathological damage of lung tissue was detected and evaluated using hematoxylin-eosin (H&E) staining. The expression of various inflammatory factors and oxidative stress-related factors was detected using cytometric bead array (CBA) and enzyme-linked immunosorbent assay (ELISA), respectively. The indicators characterizing intestinal barrier damage were detected through the application of Alcian blue periodic acid Schiff (AB-PAS) staining, ELISA, and western blot. Furthermore, gut microbiota were analyzed by 16S rRNA, and serum and lung metabolites were analyzed by metabolomics. Finally, proteomics was applied to enrich key signaling pathways, and western blot was used to validate the relevant proteins.</p><p><strong>Results: </strong>Fifty-five active components in CY were identified. The pharmacological results showed that CY significantly alleviated lung pathological injury and inflammatory response of lung tissue in ALI mice while improving the integrity of intestinal structure and the permeability of the mucosal barrier in ALI mice. The evaluation was based on the improvement of abnormal expression of inflammatory factors, oxidative stress factors, tight junction proteins, goblet cells, LPS, secretory immunoglobulin A (SIgA), diamine oxidase (DAO), and D-lactic acid (D-LA), to a certain extent. Furthermore, 16S rRNA and metabolomics results showed that multiple core bacterial genera and unsaturated fatty acids were involved during CY treatment. Finally, proteomic results indicated that the Wnt/β-catenin pathway was the mechanism of action for CY treatment of ALI, and CY effectively regulated the protein levels of Wnt3a, β-catenin, and phosphorylated glycogen synthase kinase-3β (p-GSK3β).</p><p><strong>Conclusion: </strong>This study confirmed that CY could exert pharmacological effects on improving ALI mice through the gut-lung axis and also found that core bacterial genera and unsaturated fatty acids were involved in this process. More importantly, the Wnt/β-catenin signaling pathway had been identified as a key signaling pathway for CY to alleviate ALI.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e7225946"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13581059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148156816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crohn's Disease Phenotype in a Patient With Severe Congenital Neutropenia Caused by CSF3R Variants: Exploring the Pathogenesis and Effects of Thalidomide Treatment.","authors":"Yanqiu Wang, Lin Wang, Chun Pan, Zhiheng Huang, Ping Li, Xiaoxia Qiu, Cuifang Zheng, Ying Huang","doi":"10.1155/jimr/8163275","DOIUrl":"10.1155/jimr/8163275","url":null,"abstract":"<p><p>This study describes a case of severe congenital neutropenia (SCN) harboring biallelic CSF3R variants and presenting with a novel inflammatory bowel disease (IBD) phenotype that responded remarkably to thalidomide. We performed functional studies to reveal the pathogenicity of the CSF3R and to elucidate the potential mechanisms underlying the therapeutic effects of thalidomide. A comprehensive review of the literature identified 18 reported cases of SCN associated with CSF3R variants. We subsequently validated the pathogenicity of the variants in the patient's peripheral blood by flow cytometry, which demonstrated reduced granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) expression and markedly decreased phosphorylation of signal transducer and activator of transcription (STAT)3 (p-STAT3) following stimulation with recombinant human G-CSF (rhG-CSF). Thalidomide augmented rhG-CSF-induced STAT3 phosphorylation in HEK293T cells harboring the CSF3R Q257  ^∗ or R308G/Q257  ^∗ variants, and this effect was suppressed by a Janus kinase (JAK)1 inhibitor. Thus, IBD might represent a novel phenotype of SCN caused by CSF3R variants, and thalidomide could potentially alleviate the symptoms by modulating the JAK1/STAT3 signaling pathway.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e8163275"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13389440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Divergences Between the Skin Sensitizer 2,4-Dinitrochlorobenzene and the Respiratory Sensitizer Phthalic Anhydride Revealed by Mouse Single-Cell Transcriptomics.","authors":"Mélanie Mourot-Bousquenaud, Elsa Gratianne Guillot, Amélie Coiscaud, Julianne Mathiot, Samuel Muller, Quentin Fort, Sandrine Jacquenet, Fabrice Battais","doi":"10.1155/jimr/7515115","DOIUrl":"10.1155/jimr/7515115","url":null,"abstract":"<p><strong>Background: </strong>Chemical-induced sensitization is a major health concern. To date, no internationally accepted method is able to discriminate a skin from a respiratory sensitizer. The identification of an immune profile specific to skin or respiratory sensitizers is therefore scientifically relevant.</p><p><strong>Methods: </strong>Female BALB/c mice were dermally exposed to a skin (2,4-dinitrochlorobenzene, DNCB) or to a respiratory sensitizer (phthalic anhydride, PA) at day 0 (D0) and D5 to initiate allergic sensitization and at D10, D11, and D12 to induce elicitation. Auricular lymph nodes (LNs) were collected at D0, D3, D7, D10, and D13. Single-cell transcriptomic and flow cytometric analyses were performed in order to identify immune cell proportions and marker expression. Enrichment analyses were performed at D13 on dendritic and T cells. Cytokine measurements were performed in LN cells' supernatant by bead array cytometry.</p><p><strong>Results: </strong>Exposure to both sensitizers induced a strong immune reaction demonstrated by an increase of mature B cells and an evolution of the T cell subpopulations, with an increase of follicular and memory T cells. The proportion of NKT, Th2, and Th9 cells and the levels of IgE increased specifically during PA exposure. Follicular, memory, and helper T cells showed distinct transcriptomic responses to DNCB or PA. The proportion of dendritic cells (DCs) strongly increased starting from D10 in mice exposed to DNCB, and those cells showed a specific transcriptomic signature towards the skin sensitizer. Enrichment analyses suggested a metabolic shift in DCs exposed to DNCB. Single-cell transcriptomic data were confirmed by flow- and bead array cytometry.</p><p><strong>Conclusion: </strong>A distinct transcriptomic signature was identified in immune cells during sensitization to DNCB or PA in this study.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e7515115"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of IFN-γ-Mediated Immune Cell Crosstalk in the Pathogenesis of Aplastic Anemia.","authors":"Shuai Tan, Yumeng Li, Yaochi Chen, Wanling Sun","doi":"10.1155/jimr/2216487","DOIUrl":"10.1155/jimr/2216487","url":null,"abstract":"<p><p>Interferon-gamma (IFN-γ) is a central mediator of immune-driven bone marrow failure (BMF) in acquired aplastic anemia (AA). Persistent IFN-γ signaling alters the bone marrow microenvironment by activating the JAK-STAT1 pathway, which results in immunological imbalance, inflammatory amplification, and depletion of hematopoietic stem and progenitor cells (HSPCs). IFN-γ disturbs HSPC quiescence and self-renewal, interferes with thrombopoietin (TPO)-c-Mpl communication, and stimulates cytotoxic T-cell-dominant immunological responses. Simultaneously, IFN-γ destabilizes local immunological homeostasis by disrupting immune crosstalk through the IDO1 axis and regulatory T-cell (Treg) malfunction. In addition to discussing new therapeutic methods, such as Treg-based therapies and JAK inhibition, as prospective precision approaches for AA, this review incorporates current mechanistic insights into IFN-γ-driven cellular interactions inside the bone marrow niche.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e2216487"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lnc-CHRM4-2:1 Inhibits M2 Polarization and Efferocytosis of Macrophages by Downregulating MerTK and SLC2A1 in Rheumatoid Arthritis.","authors":"Jinjin Chu, Jie Zang, Lili Zhang, Zhuojian Qu, Haibo Li, Chunjuan Yang, Jiamei Sun, Linlin Gai, Xuecheng Sun, Donghua Xu","doi":"10.1155/jimr/1718207","DOIUrl":"10.1155/jimr/1718207","url":null,"abstract":"<p><strong>Objective: </strong>Rheumatoid arthritis (RA) is a common chronic and systemic autoimmune disease. Long noncoding RNAs (lncRNAs) have been documented to play important roles in the pathogenesis of RA. This study is aimed to investigate the differentially expressed lncRNAs in RA and explore the underlying roles and mechanisms of RA-specific lncRNAs.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells (PBMCs) from three RA patients and three healthy controls were detected by transcriptome sequencing analysis. Enrichment analysis was performed to identify the potential functional categories and signal pathways. The expressions of the screened dysregulated lncRNAs in RA were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of the candidate lncRNA lnc-CHRM4-2:1 on the proliferation and apoptosis of Raw264.7 cells were determined by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) proliferation assays, and Annexin V-APC/PI staining flow cytometry assay. qRT-PCR and western blot were performed to detect the expression of functional molecules related to M1/M2 macrophage polarization and efferocytosis.</p><p><strong>Results: </strong>The expression of lnc-CHRM4-2:1 was significantly higher in PBMCs of RA patients compared to healthy controls. Lnc-CHRM4-2:1 was negatively associated with the level of serum CCP of RA patients, suggesting that it was a RA-specific lncRNA. Overexpression of lnc-CHRM4-2:1 could potentially affect cell proliferation and apoptosis, promote M1 polarization, inhibit M2 polarization, and the mRNA and protein expressions of MerTK and SLC2A1 in Raw264.7 cells.</p><p><strong>Conclusion: </strong>Lnc-CHRM4-2:1 is an RA-specific lncRNA, which inhibits macrophage M2 polarization and efferocytosis by downregulating MerTK and SLC2A1. Lnc-CHRM4-2:1 may be considered a potential diagnostic biomarker and therapeutic target for RA.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e1718207"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Glycyrrhizin Attenuates Toll Like Receptor-2, -4 and Experimental Vasospasm in a Rat Model.","authors":"Journal Of Immunology Research","doi":"10.1155/jimr/9817675","DOIUrl":"10.1155/jimr/9817675","url":null,"abstract":"","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e9817675"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Antiviral and Type 3 Immune Responses in Crush Injury Patients With Earthquake-Related Trauma.","authors":"Recep Civan Yuksel, Busra Seniz Demir, Mohammad Ahmad Houran, Mine Asan, Sahin Temel, Ahmet Safa Kaynar, Birkan Ulger, Tutkun Talih, Aliye Esmaoglu, Murat Sungur, Kürşat Gündoğan, Ahmet Eken","doi":"10.1155/jimr/7908547","DOIUrl":"10.1155/jimr/7908547","url":null,"abstract":"<p><strong>Background: </strong>Infections are frequent in critically ill patients with earthquake-associated crush injury (CI) and contribute to poor outcomes, yet the immune pathways underlying posttrauma susceptibility remain poorly defined. We investigated longitudinal changes in damage-associated molecular pattern (DAMP)/PAMP sensing and downstream inflammatory programs in CI patients requiring intensive care.</p><p><strong>Methods: </strong>Nineteen CI patients admitted to the ICU after the February 6, 2023 Kahramanmaraş earthquake and 18 age- and sex-matched healthy controls were enrolled. Peripheral blood was collected on hospital days 7 and 21. DAMP/PAMP receptor expression was assessed by flow cytometry and RT-qPCR, and pathway activation was evaluated by phospho-flow (pSTING, pIRF3, pNF-κB, and p-cJun) in gated lymphocytes and monocytes. Plasma cytokines/alarmins and select DAMPs were quantified by multiplex enzyme-linked immunosorbent assay (ELISA)/assays.</p><p><strong>Results: </strong>CI patients demonstrated broad remodeling of nucleic acid-sensing programs, including reduced expression of TLR7, STING, and IRF7, with a discordant signaling pattern characterized by increased IRF3 phosphorylation, transiently reduced pSTING, and sustained reduction of p-cJun, while NF-κB activation remained comparatively stable. In plasma, IL-33 and IFN-α2 were reduced on Day 7, and type 3 immunity-associated cytokines IL-23 and IL-17A were significantly decreased by Day 21, consistent with impaired antimicrobial barrier-supporting responses. Circulating DAMPs were dynamically altered, with increased S100A9 and HMGB1 and decreased ATP following injury.</p><p><strong>Conclusions: </strong>Earthquake-associated CI is associated with dynamic DAMP release and dysregulated innate sensing accompanied by suppression of antiviral and type 3 immune cytokine programs. These immune alterations may contribute to heightened vulnerability to secondary infections in critically ill CI patients.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2026 1","pages":"e7908547"},"PeriodicalIF":3.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13519304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148829464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}