Journal of Leukocyte Biology最新文献

{"title":"Complexity of the neutrophil transcriptome in early and severe rheumatoid arthritis: a role for microRNAs?","authors":"Michele Fresneda Alarcon, Genna Ali Abdullah, John Alexander Beggs, Isobel Kynoch, Andrew Sellin, Andrew Cross, Sam Haldenby, Philipp Antczak, Eva Caamaño Gutiérrez, Helen Louise Wright","doi":"10.1093/jleuko/qiaf090","DOIUrl":"10.1093/jleuko/qiaf090","url":null,"abstract":"<p><p>Neutrophils are innate immune cells that drive the progression of rheumatoid arthritis through the release of reactive oxygen species, neutrophil extracellular traps, and proteases that damage host tissues. Neutrophil activation is regulated, in part, by dynamic changes in gene expression. In this study, we have used RNAseq to measure the transcriptomes of neutrophils from people with severe, methotrexate-refractory rheumatoid arthritis and healthy controls. We identified a dynamic gene expression profile in people with severe rheumatoid arthritis. This is dominated by a type-I interferon-induced gene expression signature as well as activation of genes regulating neutrophil degranulation, neutrophil extracellular trap production, response to reactive oxygen species, and oxidative stress. While we did not detect significantly elevated levels of interferon-alpha in rheumatoid arthritis blood sera, we identified increased expression in rheumatoid arthritis neutrophils of miR-96-5p and miR-183-5p, which regulate activation of the interferon pathway as members of the miR-183C cluster. We also detected significantly elevated neutrophil extracellular trap debris in rheumatoid arthritis blood sera (P < 0.05). Using gene set variation analysis, we explored the heterogeneity of neutrophil gene expression in rheumatoid arthritis and identified subsets of patients with gene expression profiles reflecting enhanced neutrophil degranulation and cytotoxicity, tissue inflammation, or activation by interferons. Comparison with published single-cell RNAseq datasets identified rheumatoid arthritis transcriptomes where neutrophils were polarized by genes relating to early or late cell maturity, with significant genes in each polarized state being regulated by miR-146a-5p, miR-155-5p, miR-183-5p, or miR-96-5p. Overall, our study demonstrates the heterogeneity of the rheumatoid arthritis neutrophil transcriptome and proposes microRNA-driven mechanisms for regulating the activated neutrophil phenotype in rheumatoid arthritis.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"117 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540515","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":"Interferon regulatory factor 8 induces intrinsic functional changes in mature neutrophils.","authors":"Laura Polmann, Janna Carina Grimm, Johannes Roth, Katarzyna Barczyk-Kahlert","doi":"10.1093/jleuko/qiaf078","DOIUrl":"10.1093/jleuko/qiaf078","url":null,"abstract":"<p><p>Neutrophils are the first line of host defense. Neutrophils target invading pathogens by phagocytosis, generation of reactive oxygen species (ROS), neutrophil extracellular trap formation (NETosis), and cytokine production. Interferon regulatory factor 8 (IRF8) plays a central role in the regulation of myeloid cells fate, promoting monocyte and dendritic cell development while inhibiting neutrophil production. The global IRF8 deficiency leads to an accumulation of immature myeloid cells, mostly neutrophils, while IRF8 deficiency restricted to myeloid cells has no effect on myeloid cell differentiation. However, the role of IRF8 in regulating neutrophil function remains to be fully elucidated, especially due to the fact that IRF8 is not expressed in mature neutrophils. This study aims to investigate the impact of IRF8 on effector functions of neutrophils. The absence of IRF8 resulted in a diminished response of neutrophils to inflammatory challenge by lipopolysaccharide (LPS), as evidenced by reduced expression of inflammatory cytokines. This effect was intrinsic to IRF8-/- neutrophils and not driven by extrinsic factors, as assessed comparing bone marrow-derived and estrogen receptor-regulated homeobox B8-derived IRF8-/- neutrophils and was accompanied by reduced p38, extracellular signal-regulated kinase 1/2, and mitogen-activated protein kinase-activated protein kinase 2 activation. It is noteworthy that not all effector functions were affected by IRF8 deficiency. The mechanisms of pathogen elimination, such as phagocytosis and ROS production, were impaired in IRF8-/- neutrophils, whereas processes like NETosis remained entirely intact. In conclusion, our findings suggest that IRF8 shapes the neutrophil response to LPS and modulates neutrophil function, and this process is independent of external factors.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in age-related cardiac and splenic S100A9 and NLRP3 expression.","authors":"Kathleen Pappritz, Isabel Voss, Muhammad El-Shafeey, Sophie Van Linthout","doi":"10.1093/jleuko/qiaf031","DOIUrl":"10.1093/jleuko/qiaf031","url":null,"abstract":"<p><p>Age is an important risk factor for cardiovascular diseases and is associated with a systemic, low-grade inflammation, so-called inflammaging. We aimed to investigate the impact of age and sex on the inflammatory markers S100A9 and components of the NLRP3 inflammasome at an early stage in the aging process, using mature adult and middle-aged/perimenopausal mice. Given the importance of the cardiosplenic axis in heart failure, the spleen was analyzed in addition to the left ventricle and cardiac fibroblasts. Using immunohistochemistry, flow cytometry, and gene expression analysis, our study demonstrates a higher inflammatory state of the spleen in perimenopausal vs age-matched males and 3-mo-old female mice, whereas aging is associated with higher left ventricular gene expression of S100A9 and NLRP3 inflammasome components independent of sex. In conclusion, our data indicate that inflammatory signatures in the spleen and left ventricle already differ in middle-aged mice and are partly sex dependent.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fever-range temperature alters continual efferocytosis mediated by mouse proinflammatory macrophages.","authors":"Mathieu Vetter, Melissa Maraux, Francis Bonnefoy, Ludivine Dal Zuffo, Baptiste Lamarthée, Gwnenaël Rolin, Audrey Wetzel, Sylvain Perruche, Paul Peixoto, Philippe Saas","doi":"10.1093/jleuko/qiaf061","DOIUrl":"10.1093/jleuko/qiaf061","url":null,"abstract":"<p><p>Fever, a cardinal sign of inflammation, has been shown to modulate macrophage functions. Here, we investigate whether fever affects macrophage efferocytosis. This process is essential for the resolution of inflammation and the return to homeostasis with the reprogramming of macrophages toward a proresolving phenotype. Using primary mouse bone marrow-derived macrophages stimulated with lipopolysaccharide and interferon-γ (ie proinflammatory macrophages), we first validated that exposure to febrile temperature (39.5 °C) induced a heat shock protein response. Then, we observed that febrile temperature decreased the capacity of proinflammatory macrophages to uptake apoptotic cells. This reduced efferocytic capacity of macrophages exposed to febrile temperature resulted from a decreased capacity to interact with apoptotic cells and to internalize these dying cells. Exposure to febrile temperature reduced the cell motility of macrophages in response to apoptotic cells, as assessed by IncuCyte live-cell imaging. RNA sequencing analysis of proinflammatory macrophages exposed to febrile temperature identified an upregulation of the Adam17 gene. As this gene encodes a protease that sheds the efferocytic receptor Mer, we determined cell surface expression of Mer and quantified soluble Mer in the culture supernatants of proinflammatory macrophages exposed to febrile temperature. While febrile hyperthermia induced the Mer cleavage from the cell surface of proinflammatory macrophages, ADAM17 inhibition during exposure to febrile temperature did not restore the efferocytic capacity of proinflammatory macrophages. Thus, reduction of Mer expression induced by hyperthermia did not represent the main mechanism explaining reduced efferocytosis. Nevertheless, our work suggests that fever, by decreasing the efferocytic capacity of macrophages, maintains their proinflammatory state.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The universal receptive system: a novel regulator of antimicrobial and anticancer compound production by white blood cells.","authors":"Victor Tetz, Kristina Kardava, Maria Vecherkovskaya, Alireza Khodadadi-Jamayran, Aristotelis Tsirigos, George Tetz","doi":"10.1093/jleuko/qiaf085","DOIUrl":"10.1093/jleuko/qiaf085","url":null,"abstract":"<p><p>Despite recent advances, the regulation of anticancer and antimicrobial bioactive compound (AABC) production by leukocytes remains poorly understood. Here, we demonstrate that inactivation of the DNA- and RNA-based Teazeled receptors of the Universal Receptive System in human leukocytes generated so called \"Leukocyte-Tells,\" which showed enhanced AABC production. Comprehensive analysis of the AABCs produced by Leukocyte-Tells based on LC/MS identified 707 unique or differentially produced peptide or nonpeptide metabolites. Functional testing demonstrated that many of these metabolites exhibited increased antibacterial, antifungal, and anticancer activities. The AABCs produced by the Leukocyte-Tells were effective against different multidrug-resistant clinical isolates of fungi and gram-positive and gram-negative bacteria (including their biofilms), as well as various cancer cell lines, with >100,000-fold activity than AABCs derived from control leukocytes. Notably, the AABCs produced by the Leukocyte-Tells exhibited greater stability under adverse environmental conditions. Our findings highlight the important role of the Universal Receptive System in regulating AABC production through a process named here as cell genome-memory management, offering new insights into immune functions and suggesting potential therapeutic applications.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The release of NETs during SFTSV infection downregulates the specific inflammatory factors that lead to liver and spleen damage.","authors":"Xuewen Ji, Xinyi Yu, Zihan Xiao, Ruonan Zhang, Zihan Wu, Xinrui Zhang, Chunhui Wang, Jin Zhu, Ye Yang, Tingting Zhou","doi":"10.1093/jleuko/qiaf053","DOIUrl":"10.1093/jleuko/qiaf053","url":null,"abstract":"<p><p>Severe fever with thrombocytopenia syndrome is a life-threatening condition that has been the focus of attention in recent years. It is primarily caused by uncontrolled replication of a novel Bunyavirus and an intense proinflammatory response. NETosis is a form of cell death initiated by neutrophils, involving the formation of neutrophil extracellular traps. These neutrophil extracellular traps are composed of DNA fibers or nuclear chromatin that trap cytoplasmic granule proteins and histones in a meshwork to capture and eliminate pathogens. Our investigation delved into single-cell sequencing data from patients with severe fever with thrombocytopenia syndrome, revealing that severe fever with thrombocytopenia syndrome virus can trigger NETosis in both cellular and animal models. Furthermore, we examined the impact of neutrophil extracellular traps on Thp-1 cells through transcriptome sequencing and evaluated tissues in infected animal models, unveiling a significant downregulation of specific inflammatory factors. By integrating previous research, we propose a hypothesis that the reduction of these inflammatory factors hinders the occurrence of immune responses and the process of organ repair, thereby causing tissue damage.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-125b-5p sensitizes colorectal cancer to anti-PD-L1 therapy by decreasing TNFR2 expression on tumor cells.","authors":"Yibo Chen, Mengmeng Jiang, Ping Liao, Yang Yang, Zhonghao Chen, Yang Gao, Yiru Wang, Chon-Kit Chou, Xin Chen","doi":"10.1093/jleuko/qiaf059","DOIUrl":"10.1093/jleuko/qiaf059","url":null,"abstract":"<p><p>The microRNA miR-125b-5p, recognized as a tumor suppressor, has demonstrated the ability to curb the proliferation of various types of cancer cells. Our latest research has revealed that miR-125b-5p also impedes the proliferation and functionality of CD4 + Foxp3+ regulatory T cells by reducing the expression of tumor necrosis factor receptor 2 (TNFR2) on regulatory T cells. To explore the potential of miR-125b-5p to suppress tumor growth by targeting TNFR2 on cancer cells, we overexpressed the levels of miR-125b-5p in mouse colorectal cancer cells. Our findings showed that the overexpression of miR-125b-5p significantly suppressed the proliferation, migration, and invasiveness of TNFR2-expressing cancer cells. This was further supported by in vivo observations, in which we noted a regression of 20% to 30% of tumors in immunocompetent mice that had been treated with miR-125b-5p-overexpressing cells. Remarkably, when combined with anti-PD-L1 therapy, the regression rate increased dramatically, with over 85% of mice showing a 2- to 3-fold enhancement in tumor regression. This synergistic effect was attributed to the miR-125b-5p-mediated increase in cytotoxic CD8+ T cells. In conclusion, our study suggests that miR-125b-5p, by inhibiting TNFR2 expression in colorectal cancer cells, can enhance the effectiveness of anti-PD-L1 immunotherapy. This is achieved by modulating anti-tumor immune responses. The potential of miR-125b-5p to boost the efficacy of immunotherapies in clinical settings is a promising avenue for future therapeutic development.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage polarization, inflammatory monocytes, and impaired MDSCs are associated with murine and human immune aplastic anemia.","authors":"Joshua Glass, Xingmin Feng, Jichun Chen, Jibran Durrani, Zhijie Wu, Shouguo Gao, Ruba Shalhoub, Liangliang Wu, Neal S Young","doi":"10.1093/jleuko/qiaf073","DOIUrl":"10.1093/jleuko/qiaf073","url":null,"abstract":"<p><p>Immune-mediated bone marrow failure (BMF) entails a complex immune landscape. Myeloid cells, including monocytes, macrophages, and myeloid-derived suppressor cells (MDSCs), are involved in the development and progression of immune aplastic anemia (AA). We used a murine model of BMF to explore the effects of CSF-1R inhibition on immune pathophysiology. Hematopoiesis, immune cell populations, and gene expression were assessed by flow cytometry, cytokine analysis, and single-cell RNA sequencing. CSF-1R inhibition with the small molecule PLX3397 intensified BMF in CByB6F1 mice, enhancing inflammation and macrophage polarization toward the proinflammatory M1 phenotype. This was accompanied by increased leukocyte apoptosis, a reduction in CD11b + myeloid cells, and worsened animal survival. In contrast, the JAK inhibitor baricitinib attenuated BMF, promoting M2 macrophage polarization, and decreasing CD8+ T cell infiltration of bone marrow. Single-cell RNA analysis revealed upregulation of M1 signature genes in both murine BMF and also AA human samples. In patients with severe AA, there was a shift toward an M1-like monocyte phenotype, correlating with increased inflammatory cytokine expression and altered MDSC populations. These findings highlight the role of myeloid-derived cells in BMF and suggest that M1 macrophages, with defective MDSC function, contribute to disease pathogenesis and progression. Targeting macrophage polarization or MDSCs offers alternative therapeutic strategies in immune-mediated BMF.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136193","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":"Early increased monocyte-to-lymphocyte ratio as a potential biomarker of bacterial sepsis in patients with severe COVID-19.","authors":"Edna Basilio-Gálvez, Ruth Lizzeth Madera-Sandoval, Arturo Cérbulo-Vázquez, Jessica Lakshmi Prieto-Chávez, Graciela Libier Cabrera-Rivera, María Teresa García-de la Rosa, Patricia Esther Miranda-Cruz, Jesús Emmanuel Juárez-Palacios, Joseph García-Rodríguez, Julio Vázquez-Estrada, Virginia Lima-Salinas, Diana Alba-Lugo, Juan Carlos Anda-Garay, Alejandra Yarensy Macías-Gutiérrez, Luis Eduardo Martínez-Ascencio, Alejandra López-Teófilo, Laura Romero-Gutiérrez, Luis Alejandro Sánchez-Hurtado, Diana Ávila-Alberto, Nancy Rivas, Constantino López-Macías, Eduardo Antonio Ferat-Osorio, Lourdes Andrea Arriaga-Pizano","doi":"10.1093/jleuko/qiaf064","DOIUrl":"10.1093/jleuko/qiaf064","url":null,"abstract":"<p><p>Monocytes are pivotal during inflammation. Sepsis added to COVID-19 increases mortality and inflammation. However, the role of monocytes in this condition is unclear. Our aim was to determine monocyte frequencies and HLA-DR expression related to size distribution in patients with severe COVID-19 with or without sepsis. Twenty-nine patients with COVID-19, 9 patients with COVID-19 + sepsis, and 11 non-COVID nonseptic volunteers were recruited. Patients with COVID-19 + sepsis had increased monocyte count (P = 0.004) and monocyte-to-lymphocyte ratio (MLR, P = 0.01) prior to bacterial sepsis development. The monocyte-to-lymphocyte ratio had an area under the curve of 77.8%, suggesting its potential utility in predicting bacterial sepsis up to 21 d before positive culture. In these patients, smaller intermediate and nonclassical monocytes expressed higher levels of HLA-DR (P < 0.05). Diminished HLA-DR expression in bigger monocytes was associated with an increase in severity and inflammatory markers (r2 values equal to or higher than ±0.4, P < 0.05). Our results suggest that the monocyte-to-lymphocyte ratio could be a potential early marker for bacterial sepsis development in patients with severe COVID-19.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":"117 6","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nervonic acid mitigates IMQ-triggered psoriasis in mice via inhibiting Th17/γδT17 cell invasion and modulating the gut microbiota.","authors":"Zishan Yang, Xiaorong Geng, Shenglan Zhang, Junjie Gao, Fengxiang Ji, Yixuan Han, Zhihao Cui, Xia Wang, Sheng Guo, Dong Yan, Tiesuo Zhao, Feng Ren, Xueshi Li, Jie Dong, Zhongwei Tian, Zhinan Yin, Xiangfeng Song","doi":"10.1093/jleuko/qiaf070","DOIUrl":"10.1093/jleuko/qiaf070","url":null,"abstract":"<p><p>Psoriasis is a persistent immune-mediated inflammatory dermatosis. The treatment of psoriasis now features natural medicine as an effective new alternative because of its notable effectiveness and few side effects. Nervonic acid (NA), a long-chain fatty acid mostly sourced from the seed oils of some wild plants, exhibits significant antidepressant and anti-inflammatory properties. Nonetheless, the pathogenic effects and mechanism of NA in the pathogenesis of psoriasis are unreported. This work demonstrated that NA markedly mitigated IMQ-triggered psoriasis-like skin inflammation and reduced the mRNA expression levels of chemokines (Cxcl1 and Ccl20) and inflammatory factors (S100a8, S100a9, IL-17, and IL-6) both in vitro and in vivo. Mechanistically, NA blocked the IL-17/IMQ-induced NF-κB and p38MAPK signaling pathways in keratinocytes or tissue lesions, downregulated Ccl20 production, and therefore disrupted positive inflammatory feedback by diminishing Th17 or γδT17 cell infiltration. Furthermore, 16s rRNA sequencing demonstrated that NA therapy significantly elevated the relative abundance of Bacteroidota, but the outcome for Mucispirillum was contrary within the gut microbiota. These bacteria are linked to the onset of psoriasis and inflammation, perhaps contributing to the alleviation of IMQ-induced lesions in mice. In conclusion, NA may alleviate dermatitis in psoriatic mice by inhibiting Th17/γδT17 cell invasion and modulating the gut microbiota. Consequently, NA stands as a highly promising choice for psoriasis treatment.</p>","PeriodicalId":16186,"journal":{"name":"Journal of Leukocyte Biology","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}