{"title":"Amphotericin B for injection triggers degranulation of human LAD2 mast cells by MRGPRX2 and pseudo-allergic reactions in mice via MRGPRB2 activation.","authors":"Xu He, Xinxin Yang, Longyu Qin, Qianqian Zhang, Xiaolan Ji, Wenjuan Tang, Yingzhuan Zhan, Yanmin Zhang","doi":"10.1007/s12026-024-09532-2","DOIUrl":"10.1007/s12026-024-09532-2","url":null,"abstract":"<p><p>Amphotericin B, a polyene macrolide antifungal agent, still plays an important role in the management of serious systemic fungal infections. Amphotericin B deoxycholate (AmBd) has been used to treat invasive fungal infections for over 60 years and remains the primary clinical formulation currently available. Anaphylactoid reactions triggered by AmBd in the clinic have been documented. However, the molecular and cellular events contributing to these reactions have not been clearly elucidated to date. This study demonstrates that the human Mas-related G protein-coupled receptor X2 (MRGPRX2) is the receptor that mediates these anaphylactoid responses. Molecular docking and cellular thermal shift assay (CETSA) indicate that AmBd exhibits potential affinity with MRGPRX2. In vitro, exposure to AmBd results in significant release of LAD2 mast cell granules and induces intracellular Ca<sup>2+</sup> mobilization as well as activation of PLC-γ/IP3R and PI3K/AKT signaling pathways. However, these phenomena are reduced in MRGPRX2-knockdown LAD2 cells. In vivo, AmBd triggers paw swelling and a rapid drop in core body temperature in wild-type (WT) mice. However, these reactions are almost absent in MRGPRB2 (the mouse homolog of MRGPRX2) knockout mice (MRGPRB2<sup>MUT</sup>, MUT). The above results suggest that AmBd activates PLC-γ/IP3R and PI3K/AKT signaling via MRGPRX2 (in human LAD2 mast cells) or MRGPRB2 (in mice), leading to the release of mast cell granules and subsequent triggering of pseudo-allergic reactions. Taken together, this study clarifies the role of MRGPRX2 in triggering pseudo-allergic reactions to AmBd and suggests that MRGPRX2 could be a potential therapeutic target for controlling these reactions.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1337-1349"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunologic ResearchPub Date : 2024-12-01Epub Date: 2024-09-25DOI: 10.1007/s12026-024-09545-x
Lu Lu, Huimin He, Jindi Feng, Zhonghui Hu, Shiyu Zhang, Lu Yang, Yuehua Liu, Tao Wang
{"title":"Post-translational modification in the pathogenesis of vitiligo.","authors":"Lu Lu, Huimin He, Jindi Feng, Zhonghui Hu, Shiyu Zhang, Lu Yang, Yuehua Liu, Tao Wang","doi":"10.1007/s12026-024-09545-x","DOIUrl":"10.1007/s12026-024-09545-x","url":null,"abstract":"<p><p>Vitiligo is a chronic dermatological condition marked by the loss of skin pigmentation. Its complex etiology involves multiple factors and has not been completely elucidated. Protein post-translational modification pathways have been proven to play a significant role in inflammatory skin diseases, yet research in the context of vitiligo remains limited. This review focuses on the role of post-translational modifications in vitiligo pathogenesis, especially their impact on cellular signaling pathways related to immune response and melanocyte survival. Current therapeutic strategies targeting these pathways are discussed, emphasizing the potential for novel treatments in vitiligo management.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1229-1237"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345939","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":"In silico and experimental potentials of 6-shogaol and meglumine antimoniate on Leishmania major: multiple synergistic combinations through modulation of biological properties.","authors":"Saeid Shahsavari, Iraj Sharifi, Ehsan Salarkia, Alireza Keyhani, Fatemeh Sharifi, Zahra Babaei","doi":"10.1007/s12026-024-09530-4","DOIUrl":"10.1007/s12026-024-09530-4","url":null,"abstract":"<p><p>Conventional therapeutic agents are no longer adequate against leishmaniasis. This complex condition continues to have a high mortality rate and public health impact. The present study aimed to explore an extensive array of experiments to monitor the biological activities of 6-shogaol, a major component of ginger, and meglumine antimoniate (MA or Glucantime®). The binding affinity of 6-shogaol and inducible nitric oxide synthase (iNOS), a major enzyme catalyzing nitric oxide (NO) from L-arginine was the source for the docking outline. The inhibitory effects of 6-shogaol, MA, and mixture were assessed using colorimetric and macrophage assays. Antioxidant activity was inferred by UV-visible spectrophotometry. Variably expressed genes were measured by quantifiable real-time polymerase chain reaction. Apoptotic and cell cycle profiles were analyzed by flow cytometry. Moreover, a DNA fragmentation assay was performed by electrophoresis and antioxidant metabolites include superoxide dismutase (SOD), catalase (CAT), and also nitric oxide (NO) by enzyme-linked immunosorbent assay. 6-shogaol and MA exhibited multiple synergistic mechanisms of action. These included a remarkable leishmanicidal effect, potent antioxidative activity, a high safety index, upregulation of M1 macrophages/Th1-associated cytokines (including, γ-interferon, interleukin-12p40, tumor necrotizing factor-alpha, and associated iNOS), significant cell division capture at the sub-G0/G1 phase, a high profile of apoptosis through DNA fragmentation of the nuclear components. In addition, the activity of NO was substantially elevated by treated intracellular amastigotes, while SOD and CAT activities were significantly diminished. This study is exclusive because no similar investigation has inclusively been conducted before. These comprehensive mechanistic actions form a logical foundation for additional advanced study.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1313-1326"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunologic ResearchPub Date : 2024-12-01Epub Date: 2024-10-21DOI: 10.1007/s12026-024-09551-z
Fatma Hassan Abdelraouf, Omnia DeiaaEldin Soliman, Engy Mohammad El Khateeb, Aya Erfan Mostafa
{"title":"Clinical relevance and frequency of cytoplasmic patterns observed in ANA-Hep-2: experience of Cairo University Hospitals.","authors":"Fatma Hassan Abdelraouf, Omnia DeiaaEldin Soliman, Engy Mohammad El Khateeb, Aya Erfan Mostafa","doi":"10.1007/s12026-024-09551-z","DOIUrl":"10.1007/s12026-024-09551-z","url":null,"abstract":"<p><p>Antinuclear antibodies (ANA) are the most common biomarkers observed in autoimmune diseases. Cytoplasmic staining patterns on ANA-Hep-2 are gaining recognition but with scanty information about their clinical and diagnostic role. The aim is to assess the frequency of cytoplasmic ANA patterns in autoimmune diseases, and to evaluate their possible associations with clinical diagnoses and autoantibodies. This observational cross-sectional study was conducted by examining and/or reviewing ANA by indirect immunofluorescence assay during a 13-month period. This was followed by testing the group of patients with a positive cytoplasmic staining pattern (n = 92) using the Microblot-Array ANA plus for the presence of 44 specific autoantibodies. Out of 2741 samples, 1791 (65.3%) tested negative, 845 (30.9%) tested positive nuclear staining patterns, 56 (2.0%) positive solitary cytoplasmic staining patterns, and 49 (1.8%) positive mixed nuclear and cytoplasmic patterns. Ninety-two cases (3.4% of the total cases) were analyzed using Microblot-Array ANA plus, with reticular as the most frequent cytoplasmic pattern, followed by dense fine speckled. The most frequently associated disease with reticular pattern was primary biliary cholangitis (28.9%), and the most frequently detected autoantibodies were against M2 (66.7%). The most frequently associated disease with dense fine speckled pattern was systemic lupus erythematosus (69.4%), and the most frequently detected autoantibodies were against nucleosome (57.7%) and ribosomal P0 (53.8%). This study highlights the significance of reporting cytoplasmic staining patterns and their importance in assessment of autoimmune diseases. Larger cohort studies on treatment naïve patients are recommended.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1515-1527"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunologic ResearchPub Date : 2024-12-01Epub Date: 2024-07-31DOI: 10.1007/s12026-024-09523-3
Henricus J B Janssen, Tessa C M Geraedts, Laura F C Fransen, Ingrid van Ark, Thea Leusink-Muis, Gert Folkerts, Johan Garssen, Jelle P Ruurda, Grard A P Nieuwenhuijzen, Richard van Hillegersberg, Misha D P Luyer
{"title":"Electrical vagus nerve stimulation is a promising approach to reducing pulmonary complications after an esophagectomy: an experimental rodent model.","authors":"Henricus J B Janssen, Tessa C M Geraedts, Laura F C Fransen, Ingrid van Ark, Thea Leusink-Muis, Gert Folkerts, Johan Garssen, Jelle P Ruurda, Grard A P Nieuwenhuijzen, Richard van Hillegersberg, Misha D P Luyer","doi":"10.1007/s12026-024-09523-3","DOIUrl":"10.1007/s12026-024-09523-3","url":null,"abstract":"<p><p>After esophagectomy, an imbalanced inflammatory response increases the risk of postoperative morbidity. The vagus nerve modulates local and systemic inflammatory responses, but its pulmonary branches are transected during esophagectomy as part of the oncological resection, which may account for the high incidence of postoperative (pulmonary) complications. This study investigated the effect of electrical vagus nerve stimulation (VNS) on lipopolysaccharide (LPS)-induced lung injury in rats. Rats (n = 60) were randomly assigned to a non-vagotomy or cervical vagotomy group, with VNS or without (NOSTIM). There were four non-vagotomy groups: NOSTIM and bilateral VNS with 100, 50, or 10 µA. The four vagotomy groups were NOSTIM and VNS with fixed amplitude (50 µA) bilaterally before (VNS-50-before) or after bilateral vagotomy (VNS-50-after), or unilaterally (left) before ipsilateral vagotomy (VNS-50-unilaterally). LPS was administered intratracheally after surgery. Pulmonary function, pro-inflammatory cytokines in serum, broncho-alveolar lavage fluid (BALF), and histopathological lung injury (LIS) were assessed 180 min post-procedure. In non-vagotomized rats, neutrophil influx in BALF following intra-tracheal LPS (mean 30 [± 23]; P = 0.075) and LIS (mean 0.342 [± 0.067]; P = 0.142) were similar after VNS-100, compared with NOSTIM. VNS-50 reduced neutrophil influx (23 [± 19]; P = 0.024) and LIS (0.316 [± 0.093]; P = 0.043). VNS-10 reduced neutrophil influx (15 [± 6]; P = 0.009), while LIS (0.331 [± 0.053]; P = 0.088) was similar. In vagotomized rats, neutrophil influx (52 [± 37]; P = 0.818) and LIS (0.407 [SD ± 0.037]; P = 0.895) in VNS-50-before were similar compared with NOSTIM, as well as in VNS-50-after (neutrophils 30 [± 26]; P = 0.090 and LIS 0.344 [± 0.053]; P = 0.073). In contrast, VNS-50-unilaterally reduced neutrophil influx (26 [± 10]; P = 0.050) and LIS (0.296 [± 0.065]; P = 0.005). Systemic levels of cytokines TNF-α and IL-6 were undetectable in all groups. Pulmonary function was not statistically significantly affected. In conclusion, VNS limited influx of neutrophils in lungs in non-vagotomized rats and may attenuate LIS. Unilateral VNS attenuated lung injury even after ipsilateral vagotomy. This effect was absent for bilateral VNS before and after bilateral vagotomy. It is suggested that the effect of VNS is dependent on (partially) intact vagus nerves and that the level of the vagotomy during esophagectomy may influence postoperative pulmonary outcomes.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1247-1258"},"PeriodicalIF":3.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855358","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}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-07-23DOI: 10.1007/s12026-024-09519-z
Li Li, Feng Xu, Yi Han, Jun Zeng, Shan Du, Changshan Wang
{"title":"Thymic microenvironment's impact on immunosenescence.","authors":"Li Li, Feng Xu, Yi Han, Jun Zeng, Shan Du, Changshan Wang","doi":"10.1007/s12026-024-09519-z","DOIUrl":"10.1007/s12026-024-09519-z","url":null,"abstract":"<p><p>Age-related thymic involution is characterized by the loss of T cell development and the supporting epithelial network, which are replaced by adipose tissue. We previously showed that aging functionally impairs lymphohematopoietic progenitor cells, including thymic early T cell progenitors (ETPs), contributing to thymic involution. Considering that the thymic microenvironment is essential for thymocyte incubation, we aimed to investigate its role in age-related thymic involution and the mechanisms underlying these changes. The challenge in studying these processes led us to transplant T cell-depleted fetal thymus tissue into the kidney capsule of aged mice. This model allowed us to identify the mechanisms driving age-related changes in the thymic microenvironment and to assess whether these changes could be reversed. Flow cytometry was used to detect naïve T cells (CD62L<sup>+</sup>CD44<sup>-</sup>), including CD4 CD8 double-negative, double-positive, and single-positive T cells. Real-time PCR was used to detect and quantify signal-joint T cell receptor excision circles. We rearranged δRec-ΨJα in murine peripheral blood leukocytes to evaluate the thymic output of newly developed naïve T cells in the mice and gene expression in the thymus. Age-related thymic involution decreased naïve T cells and increased memory T cells, while fetal thymus transplantation improved thymic output and T cell production and reversed the impairment of thymopoiesis due to thymic involution in aged mice. Furthermore, the expression of key cytokines was restored and ETPs in the aged mice showed normal thymic T cell development. Our study suggests that degenerative changes in the thymic microenvironment are the primary cause of thymic dysfunction, leading to immunosenescence associated with age-related thymic involution.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1161-1173"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-07-29DOI: 10.1007/s12026-024-09509-1
Wei Shen, Yibo Liang, Dong Lv, Nan Xie
{"title":"Novel insights into the heterogeneity of FOXP3 + Treg cells in drug-induced allergic reactions through single-cell transcriptomics.","authors":"Wei Shen, Yibo Liang, Dong Lv, Nan Xie","doi":"10.1007/s12026-024-09509-1","DOIUrl":"10.1007/s12026-024-09509-1","url":null,"abstract":"<p><p>This study uncovers the novel heterogeneity of FOXP3 + regulatory T (Treg) cells and their pivotal role in modulating immune responses during drug-induced allergic reactions, employing cutting-edge single-cell transcriptomics. We established a mouse model for drug-induced allergic reactions and utilized single-cell RNA sequencing (scRNA-seq) to analyze the transcriptomic landscapes of FOXP3 + Treg cells isolated from affected tissues. The study involved both in vitro and in vivo approaches to evaluate the impact of FOXP3 expression levels on the immunoregulatory functions of Treg cells during allergic responses. Techniques included flow cytometry, cluster analysis, principal component analysis (PCA), CCK8 and CSFE assays for cell proliferation, LDH release assays for toxicity, ELISA for cytokine profiling, and CRISPR/Cas9 technology for gene editing. Our findings revealed significant transcriptomic heterogeneity among FOXP3 + Treg cells in the context of drug-induced allergic reactions, with distinct subpopulations exhibiting unique gene expression profiles. This heterogeneity suggests specialized roles in immune regulation. We observed a decrease in the proliferative capacity and cytokine secretion of FOXP3 + Treg cells following allergic stimulation, alongside an increase in reaction toxicity. Manipulating FOXP3 expression levels directly influenced these outcomes, where FOXP3 deletion exacerbated allergic responses, whereas its overexpression mitigated them. Notably, in vivo experiments demonstrated that FOXP3 overexpression significantly reduced the severity of allergic skin reactions in mice. Our study presents novel insights into the heterogeneity and crucial immunoregulatory role of FOXP3 + Treg cells during drug-induced allergic reactions. Overexpression of FOXP3 emerges as a potential therapeutic strategy to alleviate such allergic responses. These findings contribute significantly to our understanding of immune regulation and the development of targeted treatments for drug-induced allergies.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1071-1085"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-06-03DOI: 10.1007/s12026-024-09501-9
Ilaria Mormile, Maria Celeste Gigliotti, Anne Lise Ferrara, Roberta Gatti, Giuseppe Spadaro, Amato de Paulis, Stefania Loffredo, Maria Bova, Angelica Petraroli
{"title":"Clinical features and potential markers of disease in idiopathic non-histaminergic angioedema, a real-life study.","authors":"Ilaria Mormile, Maria Celeste Gigliotti, Anne Lise Ferrara, Roberta Gatti, Giuseppe Spadaro, Amato de Paulis, Stefania Loffredo, Maria Bova, Angelica Petraroli","doi":"10.1007/s12026-024-09501-9","DOIUrl":"10.1007/s12026-024-09501-9","url":null,"abstract":"<p><p>Idiopathic non-histaminergic acquired angioedema (InH-AAE) is a rare disease, with unknown etiology and pathogenesis, characterized by recurrent clinical manifestations and resistance to antihistamines and corticosteroids. We aim to evaluate clinical features and potential markers of disease in an Italian cohort of patients with InH-AAE. We enrolled 26 patients diagnosed with InH-AAE. Information about clinical features, treatments, routine laboratory investigations, immunological and genetic tests were collected. We assessed plasma levels of complement components, angiogenic and lymphangiogenic mediators, proinflammatory cytokines and chemokines, and activity of phospholipases A2. Finally, patients underwent nailfold videocapillaroscopy (NVC); both quantitative and qualitative capillaroscopic parameters were analyzed. Plasma levels of VEGFs were similar in healthy controls and in InH-AAE patients. ANGPT1 was decreased in InH-AAE patients compared to controls while ANGPT2 was similar to controls. Interestingly, the ANGPT2/ANGPT1 ratio (an index of vascular permeability) was increased in InH-AAE patients compared to controls. sPLA2 activity, elevated in patients with C1-INH-HAE, showed differences also when measured in InH-AAE patients. TNF-α concentration was higher in InH-AAE patients than in healthy controls, conversely, the levels of CXCL8, and IL-6 were similar in both groups. At the NVC, the capillary loops mainly appeared short and tortuous in InH-AAE patients. InH-AAE represents a diagnostic challenge. Due to the potential life-threatening character of this condition, a prompt identification of the potentially bradykinin-mediated forms is crucial. A better comprehension of the mechanism involved in InH-AAE would also lead to the development of new therapeutic approaches to improve life quality of patients affected by this disabling disease.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"991-1002"},"PeriodicalIF":4.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199833","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}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-06-15DOI: 10.1007/s12026-024-09507-3
Richa Mishra, Swati Sharma, Naveen Arora
{"title":"Flagellin conjugated Per a 10 and its T cell peptides attenuate airway inflammation and restore cellular function.","authors":"Richa Mishra, Swati Sharma, Naveen Arora","doi":"10.1007/s12026-024-09507-3","DOIUrl":"10.1007/s12026-024-09507-3","url":null,"abstract":"<p><p>Adjuvants were used to modulate response towards relevant immune cells. The present study aims to investigate FlaA-conjugated Per a 10 and T cell peptides in amelioration of allergic airway disease in mice. Mice given Per a 10 showed allergic features with higher cellular infiltration, IgE, Th-2 cytokines and alarmins. Fusion protein treatment reduced lung inflammation (p < 0.0001) and cellular infiltrates (p < 0.001) with higher IgG2a/IgE indicating resolution of disease. Immunotherapy with FPT1 and FPT3 reduces IL-4, IL-5 and IL-13 levels (p < 0.0001) with a fourfold increase in IFN-γ secretion in BALF. FPT1- and FPT3-treated mice have increased IL-10 and TGF-β levels (p < 0.001) with CD4<sup>+</sup>Foxp3<sup>+</sup> T cells (p < 0.01) indicating Treg response. There was enhanced expression of claudin-1 (1.7-fold) and occludin (fourfold) in lungs of FPT1- and FPT3-treated mice with reduced TSLP (p < 0.01) and IL-33 (p < 0.0001) secretion in BALF indicating recovery of epithelial function. Peptide-conjugated FlaA proteins showed protective immunity in mice and have potential for immunotherapy with restoration of cellular function.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1051-1060"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunologic ResearchPub Date : 2024-10-01Epub Date: 2024-07-03DOI: 10.1007/s12026-024-09512-6
Yasuhiro Shimojima, Takanori Ichikawa, Dai Kishida, Ryota Takamatsu, Yoshiki Sekijima
{"title":"HLA-E-expressing macrophage polarization and increased NKG2A/CD94 expression in adult-onset Still's disease.","authors":"Yasuhiro Shimojima, Takanori Ichikawa, Dai Kishida, Ryota Takamatsu, Yoshiki Sekijima","doi":"10.1007/s12026-024-09512-6","DOIUrl":"10.1007/s12026-024-09512-6","url":null,"abstract":"<p><p>We investigated the phenotypic characteristics of human leukocyte antigen (HLA)-E-expressing macrophages, NKG2A/CD94 expression in T and natural killer (NK) cells, and their interactions in patients with adult-onset Still's disease (AOSD). Peripheral blood mononuclear cells from 22 patients with AOSD and 22 healthy controls (HC) were used. Isolated monocytes were cultured first with macrophage colony-stimulating factor to differentiate into M0 macrophages and subsequently with lipopolysaccharide/interferon-γ or interleukin-4 to differentiate into M1 or M2 macrophages, respectively. HLA-E and NKG2A/CD94 expression levels were evaluated using quantitative RT-PCR and flow cytometry. HLA-E expression in M0 and M2 macrophages was significantly higher in patients with AOSD than in HC, and was positively correlated with serum C-reactive protein levels and erythrocyte sedimentation rate. NKG2A/CD94 expression in CD4 + and CD8 + T cells was significantly higher in patients with AOSD than in HC, but that in NK cells was not significantly different. In patients with AOSD, NKG2A expression in CD4 + T cells positively correlated with HLA-E expression in M0, M1, and M2 macrophages. CD94 expression in CD8 + T cells inversely correlated with HLA-E expression in M1 and M2 macrophages. NKG2A and CD94 expression in NK cells inversely correlated with HLA-E expression in M0, M1, and M2 macrophages. No significant correlation was observed between HLA-E and NKG2A/CD94 expression in HC. Increased expression of HLA-E in macrophages and NKG2A/CD94 in T cells can be observed in the inflammatory condition of AOSD. HLA-E-expressing macrophages may be associated with NKG2A/CD94 expression in T and NK cells with different correlations.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1108-1119"},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}