Immunity, Inflammation and Disease最新文献

{"title":"Fluvastatin Promotes Treg Cell Production in Allogeneic Immune Reaction and Suppresses Inflammatory Response","authors":"Xianxian Chen,&nbsp;Dong Huang,&nbsp;Li Zhao,&nbsp;Donghai Tang,&nbsp;Yu Tian,&nbsp;Chunxiao Ren,&nbsp;Fen Yan,&nbsp;Kailin Xu,&nbsp;Kai Zhao","doi":"10.1002/iid3.70165","DOIUrl":"https://doi.org/10.1002/iid3.70165","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Statins, a class of HMG-CoA reductase inhibitors, exhibit prophylactic benefits against immune rejection induced by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Despite the protective function is confirmed, the precise mechanism to induce immune tolerance of statin in the initial stages of transplantation remains incompletely understood. Given that Treg cells play a critical role in preventing graft versus host response and Foxp3 as a transcription factor of Treg can be induced by statins, we hypothesize that the immunosuppressive effects of statins are partially mediated through regulation of Treg cells expansion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>T cells were stimulated in vitro under anti-CD3/anti-CD28/IL-2/TGF-β condition or allo-reactive system with or without the addition of statins. The induction of Tregs were detected using flow cytometry. Allo-HSCT models were established by transferring donor cells alone or combined with recipient treated by fluvastatin. The proportions of Treg and phenotypes of effector T cells were identified. Cytokine secretion and antigen-presenting cell (APC) function were tested in irradiated mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Statins induced higher Treg production in classical and allogeneic cell co-culture conditions in vitro. In the early stage of models treated with fluvastatin only in donors or combined treatment of donors and recipients, a similar phenomenon was observed with elevated levels of Foxp3⁺ Treg along with increased expression of CCR7, CD62L, and S1P1 on allo-reactive T cells. Fluvastatin treatment suppressed the secretion of pro-inflammatory cytokines IFN-γ and TNF-α by CD4⁺ and CD8⁺ T cells in irradiated mice. Furthermore, fluvastatin also contributed to restraining the numbers and activation of APCs, including dentritic cells (DCs) and macrophages in vitro and in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our finding demonstrated that statin exposure modulates immune responses during the initial phase of allo-HSCT by promoting Treg expansion and suppressing inflammatory reactions, which supply a promising strategy for aGVHD prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70165","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143489846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes of Peripheral T Cells in Systemic Lupus Erythematosus Patients","authors":"Juanfeng Lao,&nbsp;Rongjun Huang,&nbsp;Rongcai Wu,&nbsp;Yulin Yuan","doi":"10.1002/iid3.70156","DOIUrl":"https://doi.org/10.1002/iid3.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Efficient indicators for evaluating the imbalance of lymphocyte function were crucial to clinical therapy in systemic lupus erythematosus (SLE) patients. This study aimed to find biomarkers to assess lymphocyte-mediated immune response in SLE patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 81 SLE patients (non-active: <i>n</i> = 35, active: <i>n</i> = 46) and 70 healthy donors were recruited in the study. Peripheral blood was obtained, and flow cytometry was used to detect circulating lymphocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data showed that the counts of CD3⁺T, CD4⁺T, CD8⁺ T, and NK cells were decreased in active SLE patients compared with non-active SLE patients and healthy donors. The counts of peripheral T cells were increased in responders but decreased in non-responders among active patients. In addition, an increase in B cell counts was found in active SLE patients compared with those in the other two groups. Active SLE patients showed higher percentages of memory T cells but lower naive T cells than those in non-active SLE patients and healthy controls. Activation molecules (CD38 and HLA-DR) and inhibitory molecule PD-1 expressions on T cells were significantly higher but percentages of CD28⁺CD8⁺T cells were lower in active SLE patients compared with those in the other two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study indicated that monitoring the alterations of circulating lymphocyte counts and surface molecules may be helpful to assess disease activity of SLE patients, even discriminate active and non-active patients, which was beneficial to choose the best treatment option in clinical therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Natural Killer Cell-Associated Clusters in Skin Melanoma and the Impact on Prognosis and Drug Sensitivity","authors":"Jun Zhou,&nbsp;Renhui Cai,&nbsp;Danqun Zhang,&nbsp;Caifeng Chen","doi":"10.1002/iid3.70143","DOIUrl":"https://doi.org/10.1002/iid3.70143","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skin melanoma exhibits significant heterogeneity in clinical outcomes and treatment responses among patients. This study aimed to investigate natural killer (NK) cell clusters in skin melanoma, their impact on patient prognosis, and their value as biomarkers for tailoring treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from TCGA, GSE19234, GSE65904, GSE244982, and GSE78220. A gene classifier was developed to identify two distinct clusters of melanoma patients. Survival analysis, NK cell infiltration levels, and responses to immune and targeted therapies were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Unsupervised clustering revealed two distinct melanoma patient clusters with significant differences in NK cell activity and clinical outcomes. Cluster 1 showed higher NK cell infiltration, better overall survival (OS) (<i>p</i> &lt; 0.0001), and greater activity in NK-cell-related pathways. In contrast, Cluster 2, characterized by lower NK cell activity and higher exhaustion markers, had poorer OS. Drug sensitivity analysis indicated that Cluster 1 was more responsive to most melanoma treatments, whereas Cluster 2 had higher sensitivity to trametinib (<i>p</i> &lt; 0.001). The developed gene classifier had an AUC of 0.913 and effectively differentiated between clusters. Additionally, Cluster 1 showed better responses to immunotherapy with a higher rate of complete and partial responses (<i>p</i> &lt; 0.001). These findings were validated in external databases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study identifies two distinct NK-cell-related clusters in melanoma with differential prognoses and treatment responses. These findings underscore the importance of integrating NK-cell-related profiles into personalized treatment strategies, offering a pathway to optimize therapeutic outcomes based on specific immune profiles.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143423633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent Lymphopenia as a Poor Prognostic Factor in Patients With Multiple Organ Dysfunction Syndrome in the Renal Intensive Care Unit: A Retrospective Single-Center Study","authors":"Xiang Xue,&nbsp;Shuhua Zhu,&nbsp;Shutian Xu,&nbsp;Yuchao Zhou,&nbsp;Yang Wang,&nbsp;Lixuan Lou,&nbsp;Shijun Li","doi":"10.1002/iid3.70152","DOIUrl":"https://doi.org/10.1002/iid3.70152","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Multiple organ dysfunction syndrome (MODS), defined as two or more organ dysfunction during infection or following shock or trauma, correlates with poor outcomes. Clinical data, including MODS in the renal intensive care unit (ICU), are scarce. Therefore, we investigate the clinical characteristics and prognosis of patients with MODS in the renal ICU.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single-center, retrospective cohort study of 99 adult patients with MODS admitted to the renal ICU of the National Clinical Research Center of Kidney Disease, Jinling Hospital, Nanjing, China, from October 1, 2011 to October 1, 2021.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>99 patients had a mean age of 49.7 ± 16.5 years old, and 51 (51.5%) patients died within 28 days after being admitted to the renal ICU. Infection (80 patients, 80.8%) was the most common reason for admission, with 47 cases being pulmonary infections. Of all of the 99 patients, 73 (73.7%) presented with persistent lymphocytopenia (lymphocyte count &lt; 1.1 × 10⁹/L from the day of ICU admission through to day 7), with 33 and 40 presenting moderate (lymphocyte count 0.6–1.1 × 10⁹/L) and severe persistent lymphopenia (lymphocyte count ≤ 0.6 × 10⁹/L), respectively. These patients had higher illness severity and chronic kidney disease (CKD) prevalence. Patients with severe persistent lymphopenia were associated with higher 28-day ICU mortality (87.5% vs. 42.4% vs. 7.7%, <i>p</i> &lt; 0.001) versus those with moderate and without persistent lymphopenia. Multivariable logistic regression analysis revealed that the number of organs involved, APACHE-II score, and persistent lymphopenia were independent risk factors for 28-day mortality in patients with MODS. The value of lymphocyte count on day 7 of admission in predicting poor prognosis of patients was higher than on other days (Area Under Curve, AUC = 0.831).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with MODS are critically ill with high mortality. Persistent lymphopenia is frequent in patients with MODS and is independently associated with 28-day mortality. Lymphocyte counts on day 7 of admission were shown to be highly predictive of prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hiding in Plain Sight—Relapsing Polychondritis Disguised as Hip Arthritis: A Case Report and Literature Review","authors":"Zhanxia Li,&nbsp;Tao Ren","doi":"10.1002/iid3.70159","DOIUrl":"https://doi.org/10.1002/iid3.70159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Relapsing polychondritis (RP) is a rare autoimmune disorder characterized by episodic inflammation of cartilaginous tissues. Its diverse clinical manifestations frequently pose diagnostic challenges and lead to misdiagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We present a 59-year-old female initially diagnosed with refractory hip osteoarthritis based on persistent left hip pain unresponsive to conventional anti-inflammatory therapy. Subsequent development of stridor and dyspnea prompted comprehensive evaluation, including laryngotracheal imaging, autoimmune serology, and multidisciplinary consultation. Diagnostic criteria for RP were applied in accordance with revised Michet criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Tracheal stenosis secondary to tracheal chondritis and iritis were identified, confirming the diagnosis of RP. Following initiation of corticosteroid therapy, the patient exhibited marked clinical improvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case underscores the importance of enhanced clinical awareness regarding atypical presentations of RP, particularly when accompanied by evolving systemic symptoms. A multidisciplinary diagnostic approach is advocated to facilitate early detection and improve patient outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Follow-Up of Patients With Positive Antiphospholipid Antibodies After Fetal Death: Five Typical Cases From a Prospective Cohort Study","authors":"Anxia Xie,&nbsp;Zhanmei Liu,&nbsp;Shenglan Wang,&nbsp;Mingqian Yuan,&nbsp;Ling Xie,&nbsp;Shengdong Liu,&nbsp;Xiaoxing Wei","doi":"10.1002/iid3.70158","DOIUrl":"https://doi.org/10.1002/iid3.70158","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Testing of antiphospholipid antibodies (aPLs) has attracted increasing attention for its association with thrombosis and pregnancy loss. However, few studies reported long-term monitoring outcomes of patients who experienced pregnancy loss and exhibited positivity for aPLs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We investigated the causes of fetal death in five cases with positive aPLs and traced the patients for changes in aPLs, subsequent pregnancy outcomes, and thrombotic events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This is a report of five typical cases from a prospective cohort study on the diagnosis of antiphospholipid syndrome (APS) in patients who were hospitalized for fetal death in Xining, China. Long-term follow-up was conducted and repeat aPL testing was recommended when the patients were confirmed or suspect APS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All five patients had subsequent pregnancies that resulted in term livebirths. None of the patients experienced thrombotic events. One showed progression of aPL serostatus from alone IgM of aβ2GP-1 to both IgM and IgG of aβ2GP-1, two exhibited fluctuation of aPL serostatus, and one had negative conversion, and the other one had not retested aPLs and did not receive any intervention with uneventful subsequent pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The aPLs of a patient with APS may develop or may disappear, so long-term monitoring cannot be discounted. Also, a woman who has experienced fetal death and exhibits positivity for aPLs may not necessarily be a patient with APS, as there are a variety of conditions in which aPLs appear.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70158","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Cell Analysis of Endothelial Cell Injury in IgA Nephropathy","authors":"Yong-Chang Yang,&nbsp;Lin Zhu,&nbsp;Jing-Ying Zhao,&nbsp;Bo Zhang,&nbsp;Xiao-Meng Wang,&nbsp;Wai W. Cheung,&nbsp;Cheng-Guang Zhao,&nbsp;Ping Zhou","doi":"10.1002/iid3.70149","DOIUrl":"https://doi.org/10.1002/iid3.70149","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The precise mechanisms responsible for renal injury in IgA nephropathy (IgAN) are not fully understood. Our study employed an extensive scRNA-seq analysis of kidney biopsies obtained from individuals with IgAN, with a specific emphasis on investigating the involvement of renal endothelial cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We obtained data from the Gene Expression Omnibus database and conducted bioinformatics analysis, which included enrichment analysis of differentially expressed genes, AUCell analysis, and high-dimensional weighted gene co-expression network analysis (hdWGCNA). The results of these analyses were further validated using human renal glomerular endothelial cells (HRGECs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The ScRNA-seq data uncovered notable variations in gene expression between IgAN and control kidney tissues. The enrichment analysis using AUCell demonstrated a high presence of adhesion molecules and components related to the mitogen-activated protein kinase signaling pathway within the renal endothelial cells. Furthermore, through hdWGCNA analysis, it was discovered that interleukin (IL)-6, Rac1, and cadherin exhibited associations with the renal endothelial cells. Stimulation of HRGECs with IL-6/IL-6 receptor resulted in a significant reduction in VE-cad expression while inhibiting Rac1 led to a substantial decrease in Rac1-GTP levels and an increase in VE-cad expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study presents novel findings regarding the contribution of renal endothelial cells to the development of IgAN, as it demonstrates that IL-6 negatively regulates VE-cad expression in HRGECs via Rac1. These results highlight the significant involvement of renal endothelial cells in the pathogenesis of IgAN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143396887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porphyromonas gingivalis and Its Outer Membrane Vesicles Induce Neuroinflammation in Mice Through Distinct Mechanisms","authors":"Yu Qiu,&nbsp;Yueyang Zhao,&nbsp;Guiqiong He,&nbsp;Deqin Yang","doi":"10.1002/iid3.70135","DOIUrl":"https://doi.org/10.1002/iid3.70135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) is the most common chronic neurodegenerative disorder, with neuroinflammation playing an important role in its progression to become a major research focus. The role of <i>Porphyromonas gingivalis</i> (<i>Pg</i>) and its outer membrane vesicles (<i>Pg</i> OMVs) in AD development is uncertain, particularly regarding their effects on neuroinflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The cognition of mice injected with <i>Pg</i>, <i>Pg</i> OMVs, or PBS via the tail vein was assessed by the Morris water maze test. Pathological changes in the mouse brain were analyzed via immunohistochemistry, immunofluorescence and hematoxylin‒eosin (H&amp;E) staining, and the ultrastructure of the hippocampus was observed via transmission electron microscopy (TEM). Plasma levels of inflammatory factors were assessed by enzyme-linked immunosorbent assay (ELISA). Protein levels of brain inflammatory factor, occludin, and NLRP3 inflammasome-related proteins were assessed by western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Memory impairment; notable neuroinflammation, including astrocyte and microglial activation; and elevated protein levels of IL-1β, TNF-α, and IL-6 in the hippocampus were detected in the <i>Pg</i> and <i>Pg</i> OMV groups. However, <i>Pg</i> induced weight loss and systemic inflammation, such as splenomegaly and increased IL-1β and TNF-α levels in plasma, whereas <i>Pg</i> OMVs had minimal impact. In addition, <i>Pg</i> induced more pronounced activation of the NLRP3 inflammasome compared to <i>Pg</i> OMVs. In contrast, only the <i>Pg</i> OMV group exhibited blood−brain barrier (BBB) disruption characterized by reduced integrity of tight junctions and lower levels of occludin protein.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p><i>Pg</i> is associated with a significant immune response and systemic inflammation, which in turn exacerbates neuroinflammation via activating NLRP3 inflammasome. However, <i>Pg</i> OMVs might elude the systemic immune response and disrupt tight junctions, thereby entering the brain and directly triggering neuroinflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omalizumab Treated Urticaria Patients Display T Cell and Thrombocyte-Associated Gene Regulation","authors":"Anna Smola,&nbsp;Heike C. Hawerkamp,&nbsp;Péter Oláh,&nbsp;Andreas Kislat,&nbsp;Nicole Duschner,&nbsp;Bernhard Homey,&nbsp;Stephan Meller","doi":"10.1002/iid3.70132","DOIUrl":"https://doi.org/10.1002/iid3.70132","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic spontaneous urticaria (CSU) is a debilitating inflammatory skin disease with a prevalence of approximately 1% of the population. It is characterized by recurrent itchy wheals and/or angioedema for more than 6 weeks without known triggers leading to a high quality of life impairment. The pathogenesis of CSU remains not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to explore the pathomechanism of CSU beyond mast cells and IgE-dependent histamine release and to identify possible biomarkers for the disease and its treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated a patient cohort in the first month of omalizumab treatment regarding the IgE levels and changes in gene and miRNA expression in peripheral blood. The cohort was divided into responders and nonresponders (depending on the score of the urticaria control test) and compared to a group of healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our messenger RNA and microRNA microarray analyses revealed the greatest changes in expression levels on Day 2 after the first omalizumab dose.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We identified several genes and miRNAs of interest, most of which have not been described to be linked to CSU so far, underlining, for example, to T cell involvement or even suggesting platelet involvement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of the Single-Cell Landscape of Hashimoto's Thyroiditis Tissue and Peripheral Blood by Single-Cell RNA Sequencing","authors":"Kaiyu Song,&nbsp;Xiaojie Wang,&nbsp;Wenjie Yao,&nbsp;Yuantao Wang,&nbsp;Qinling Zhang,&nbsp;Yuxiao Tang,&nbsp;Yakui Mou,&nbsp;Xicheng Song,&nbsp;Jin Zhou","doi":"10.1002/iid3.70153","DOIUrl":"https://doi.org/10.1002/iid3.70153","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, and its etiology may be related to genetic, environmental, and epigenetic factors. However, its exact pathogenesis remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, single-cell transcriptomic sequencing and bioinformatics analysis were performed on the thyroid tissues of six HT patients, peripheral blood mononuclear cells (PBMCs) of four HT patients, and normal thyroid tissue of one healthy control. A panoramic single-cell atlas of HT was constructed to explore changes in the abundance of different cell subsets in the states of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A single-cell atlas of HT was constructed, and eight cell types were defined based on the marker genes. Subsequent clustering analysis of T cells, B cells, myeloid, and thyroid follicular cells revealed that the abundance rates of the CD8⁺T_CCL4L2, B_MEF2B_BCL6, Mac_APOE, Mac_IL1B, and TFC_PAX8_NKX2-1 subgroups were elevated in thyroid tissues of HT patients. However, the abundance rate of the NKT_KLRD1_KLRC2 subgroup was risen in the PBMCs of HT patients. Ig-producing plasma cells were specifically enriched in the B-cell subgroup.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The present study further validated the role of immune cells in the pathogenesis of HT at the cellular level. In addition, a new cell subset B_MEF2B_BCL6 was found. It could be speculated that MEF2B mainly transactivates the expression level of the transcriptional repressor BCL6, leading to the development of HT. A new cell subset TFC_PAX8_NKX2-1 was also identified, in which the specific transcription factors PAX8 and NKX2-1 were highly expressed in HT tissues.</p>\u0000 </section>\u0000 </div>","PeriodicalId":13289,"journal":{"name":"Immunity, Inflammation and Disease","volume":"13 2","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iid3.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}