Scandinavian Journal of Immunology最新文献

{"title":"Central Tolerance or Central Adaptation?","authors":"Masoud H Manjili","doi":"10.1111/sji.70011","DOIUrl":"10.1111/sji.70011","url":null,"abstract":"","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"101 2","pages":"e70011"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433753","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":"Immune Checkpoint Receptor Expression Profiles of MAIT Cells in Moderate and Severe COVID-19.","authors":"Matyas Meggyes, David U Nagy, Ildiko Toth, Timoteus Feik, Beata Polgar, Iyad Saad Al Deen, David Sipos, Laszlo Szereday, Agnes Peterfalvi","doi":"10.1111/sji.70008","DOIUrl":"10.1111/sji.70008","url":null,"abstract":"<p><p>MAIT cells are one of the largest unconventional T cell populations and, recruited to the site of infection, play both protective and pathogenic roles during pulmonary viral infections. MAIT cell activation patterns change significantly during COVID-19, with a notable decrease in their frequency in peripheral blood of severe cases. In the present study, we aimed to investigate the expression profiles of various immune checkpoint pathways on MAIT, MAIT-like and non-MAIT cells in moderate and severe COVID-19 patients undergoing cytokine storm. Despite numerous studies comparing MAIT cell characteristics based on COVID-19 disease severity, none have delved into the critical differences in MAIT cell immune checkpoint profiles between moderate and severe COVID-19 patients, all experiencing a cytokine storm. Flow cytometry was used to analyse peripheral blood mononuclear cells from a cohort of 35 patients, comprising 18 moderate and 17 severe cases, alongside 14 healthy controls. Our investigation specifically focuses on severe COVID-19 presentations, revealing a marked deletion of MAIT cells. Further exploration into the regulatory dynamics of MAIT cell functionality reveals shifts in the expression profiles of critical immune checkpoint receptors, notably PD-1 and CD226. In severe COVID-19 patients, MAIT cells showed a significant decrease in the expression of CD226, whereas MAIT-like and non-MAIT cells demonstrated a significant increase in the expression of PD-1 compared to healthy individuals. The expression of the TIGIT receptor remained unaltered across all investigated groups. Our findings contribute to the existing knowledge by elucidating the changes in MAIT cell subpopulations and their potential role in COVID-19 disease severity.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"101 2","pages":"e70008"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468976","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":"Peripheral monocyte subsets are altered during gestation in oocyte donation pregnancy complicated with pre-eclampsia.","authors":"Xuezi Tian, Jia Li, Kim van Bentem, Ciska Lindelauf, Johanna M Kapsenberg, Carin van der Keur, Lisa E E L O Lashley, Vincent van Unen, Dave L Roelen, Frits Koning, Michael Eikmans, Marie-Louise P van der Hoorn","doi":"10.1111/sji.13432","DOIUrl":"10.1111/sji.13432","url":null,"abstract":"<p><p>Oocyte donation (OD) pregnancies show a higher fetal-maternal incompatibility and a higher risk of developing pre-eclampsia (PE) than autologous pregnancies. As maternal monocytes play a role in the tolerization of the allogeneic fetus, the aim of this study was to analyse monocyte phenotypes in healthy and PE OD pregnancies. We collected maternal peripheral blood at different gestational time points in healthy (n = 10) and PE (n = 5) OD pregnancies. Fetal-maternal human leukocyte antigen (HLA) mismatches were calculated. We used a 35-colour antibody panel for Aurora spectral flow cytometry to analyse the composition and surface marker expression of monocyte subsets. Expression of CD38 on intermediate monocytes significantly increased throughout gestation in healthy OD pregnancies. Compared with the healthy group, the PE group exhibited even higher CD38 expression on monocyte subsets, with statistical significance. Immune inhibiting receptors CD85j (LILRB1) and CD85d (LILRB2), as well as monocyte recruitment regulating molecules CCR2 and CD91, also showed significantly enhanced expression on monocyte subsets during PE. When comparing healthy and PE OD only in pregnancies with high HLA mismatches, the different CD38 and CD85j expression in monocyte subsets was still significant. In conclusion, in healthy OD pregnancies, the upregulated CD38 expression might reflect a proinflammatory condition specifically at the third trimester. In PE OD pregnancies, expression of both inflammatory and immune regulatory markers is increased in maternal peripheral monocyte subsets. The elevated expression of CCR2 and CD91 on these subsets might reflect monocyte chemotaxis and the effect from systemic vascular dysfunction at the late stage of PE.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"101 2","pages":"e13432"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370909","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":"The impact of cytokines and tumour-conditioned medium on the properties of murine in vitro generated myeloid-derived suppressor cells.","authors":"Mona Awad, Aleksandra Sen'kova, Marina Zenkova, Oleg Markov","doi":"10.1111/sji.70001","DOIUrl":"10.1111/sji.70001","url":null,"abstract":"<p><p>Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells playing a critical role in immune suppression. In vitro-generated MDSCs are a convenient tool to study the properties of tumour-associated MDSCs. Here, we compared six protocols for in vitro generation of functional mouse MDSCs from bone marrow progenitors. The protocols included granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination with interleukin-6 (IL-6) or granulocyte colony-stimulating factor (G-CSF), with or without a tumour-conditioned medium (TCM) derived from B16-F10 melanoma. Obtained MDSCs were characterized by morphology, phenotype, gene expression of key immunosuppressive factors, and in vitro suppression of T cell proliferation. All tested protocols yielded approximately 25% monocytic and 50% polymorphonuclear MDSCs. Protocols using IL-6 generated MDSCs with reduced maturation and differentiation status, upregulated Arg1 and Nos1 mRNA expression, increased levels of Arg-1 and TGF-β proteins and enhanced ROS production compared to the other protocols. All tested protocols yielded MDSCs that efficiently inhibited T cell proliferation in vitro, with some advantage for the GM-CSF and G-CSF + GM-CSF protocols. Interestingly, a combination of protocols with B16-F10-derived TCM resulted in the generation of MDSCs with reduced immunosuppressive properties. Our results provide valuable insights into the optimal conditions for in vitro generation of MDSCs with specific immunosuppressive properties.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"101 2","pages":"e70001"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047501","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}

{"title":"Evaluation of T-cell repertoire by flow cytometric analysis in primary immunodeficiencies with DNA repair defects.","authors":"Betul Gemici Karaaslan, Zeynep Hizli Demirkale, Isilay Turan, Sezin Aydemir, Zeynep Meric, Zuleyha Taskin, Ozgur Can Kilinc, Nihan Burtecene, Birol Topcu, Esra Yucel, Cigdem Aydogmus, Haluk Cokugras, Ayca Kiykim","doi":"10.1111/sji.70003","DOIUrl":"10.1111/sji.70003","url":null,"abstract":"<p><p>The group of patients with DNA-repair-defects increases susceptibility to infections due to impaired repertoire diversity. In this context, we aimed to investigate the TCRvβ-repertoire by flow cytometric analysis and its correlation with clinical entities in a group of IEI patients with DNA repair defects. Peripheral lymphocyte subset and TCRvβ-repertoire analyses were performed by flow cytometric analysis. The aim was to explore the changing TCR-Vβ-repertoire that can predict some clinical entities by investigating the repertoire using flow-cytometric-analysis-based TCR-Vβ and its interaction with clinical entities in a group of IEI patients with DNA repair defects. TCR-repertoire of the patients with DNA-repair-defects and healthy controls was analysed with flow-cytometer. The potential of flow-cytometric analysis of the TCR repertoire as a practical and easily accessible clinical prediction method was investigated. Thirty-nine-IEI patients with DNA-repair-defects and 15 age-matched healthy-controls were included in this study. Peripheral lymphocyte subset and TCR-Vβ repertoire analyses were performed by flow cytometry. Compared to the control group, 9 out of 24 clones (37.5%) exhibited a statistically significant reduction, while only 3 clones showed a statistically significant increase (p < 0.05). Preferential use of vβ-genes was associated with some clinical entities. Lower TCR-vβ-9 and TCR-vβ23, higher TCR-vβ7.2 were found in the patients with pneumonia (n = 13) (p = 0.018, p = 0.044 p = 0.032). AT patients with pneumonia had lower TCR-vβ-9 clone than patients without pneumonia (p = 0.008). Skewed proliferation of most TCR-vβ clones was seen DNA-repair-defects, especially AT. In addition, this study showed that preferential use of TCR-vβ genes could be predictive for some clinical entities.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"101 2","pages":"e70003"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450212","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":"Low iron transferrin saturation might be beneficial in the outcome of autologous transplant in multiple sclerosis.","authors":"Miranda Melgar-de-la-Paz, Moisés Manuel Gallardo-Pérez, Luis Enrique Hamilton-Avilés, Paola Negrete-Rodríguez, Danae García-Vélez, Gloria Erendy Cruz-Pérez, Sofía Chávez-Martínez, Juan Carlos Olivares-Gazca, Solón Javier Garcés-Eisele, Guillermo J Ruiz-Delgado, Guillermo J Ruiz-Argüelles","doi":"10.1111/sji.70007","DOIUrl":"https://doi.org/10.1111/sji.70007","url":null,"abstract":"","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"101 2","pages":"e70007"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425745","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}

{"title":"Vitamin D₃-VDR and vitamin A-RAR affect IL-13 and IFNγ secretion from human CD4⁺ T cells directly and indirectly via competition for their shared co-receptor RXR.","authors":"Tiana Stanisic, Emma Uttrup Ewing, Alma Lindell, Fatima Al-Jaberi, Martin Kongsbak-Wismann","doi":"10.1111/sji.13429","DOIUrl":"10.1111/sji.13429","url":null,"abstract":"<p><p>The effects of vitamin D and vitamin A in immune cells are mediated through the vitamin D receptor (VDR) and retinoic acid receptor (RAR), respectively. These receptors share the retinoid X receptor (RXR) co-factor for transcriptional regulation. We investigated the effects of active vitamin D₃ (1,25(OH)₂D₃) and 9-cis retinoic acid (9cRA) on T helper (T_H)1 and T_H2 cytokines and transcription factors in primary human blood-derived CD4⁺ T cells. We aimed to address the discrepancies in this field, particularly regarding the effects of 9cRA and the vitamins in combination. 1,25(OH)₂D₃ upregulated IL-13 and suppressed IFNγ, while 9cRA had the opposite effects. This was largely independent of a T_H1/T_H2 phenotype shift. Combined vitamin supplementation produced intermediate cytokine levels, not only through transcriptional regulation by VDR-RXR and RAR-RXR but also through 1,25(OH)₂D₃ counteracting the effects of 9cRA on solely 9cRA-responsive genes. Similar results were observed in hereditary vitamin D-resistant rickets (HVDRR) patient T cells, where VDR cannot bind to DNA, indicating that RXR binding to either receptor can limit the other's activity. Additionally, we observed downregulated RAR upon 9cRA supplementation and its re-localization out of the nucleus upon 1,25(OH)₂D₃ supplementation, suggesting a mechanism of indirect regulation by VDR. VDR protein levels were also upregulated upon 9cRA supplementation, suggesting a novel negative feedback mechanism of 9cRA transcriptional activity, whereby 9cRA promotes its own competitor. This study sets the stage for future research into the combined immunomodulatory mechanisms of 1,25(OH)₂D₃ and 9cRA, involving both direct transcriptional regulation and indirect regulation via RXR competitive binding.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"101 1","pages":"e13429"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010965","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}

{"title":"Substance P and neurokinin 1 receptor boost the pathogenicity of granulocyte-macrophage colony-stimulating factor-producing T helper cells in dry eye disease.","authors":"Hua Rong, Hai Yang, Qingqing Liu, Hui Zhang, Shaolin Wang","doi":"10.1111/sji.13434","DOIUrl":"10.1111/sji.13434","url":null,"abstract":"<p><p>Dry eye disease (DED) is an inflammatory disorder in which CD4⁺ T cells play a significant role in its pathogenesis. A CD4⁺ T cell subset termed granulocyte-macrophage colony-stimulating factor-producing T helper (ThGM) cells would contribute to DED pathogenesis. However, the mechanisms by which the activity of ThGM cells is modulated are not thoroughly understood. In this research, we characterized the effects of neurokinin 1 receptor (NK1R) and neurokinin 2 receptor (NK2R) on ThGM cells and T helper 1 (Th1) cells in a murine DED model. We found that ThGM cells expressed NK1R and NK2R, whereas Th1 cells predominantly expressed NK1R. Furthermore, substance P and neurokinin A (NKA), the ligands of NK1R and NK2R, were upregulated in post-DED LNs and conjunctivae. Substance P significantly promoted granulocyte-macrophage colony-stimulating factor (GM-CSF) expression while mildly upregulating the expression of interferon-gamma (IFN-γ) and interleukin 2 (IL-2) in ThGM cells. By contrast, NKA did not change GM-CSF expression but significantly increased IFN-γ expression in ThGM cells. Importantly, the adoptive transfer of NK1R-expressing ThGM cells significantly exacerbated DED, whereas the transfer of NK1R-knockdown ThGM cells weakly aggravated DED. NK2R knockdown in ThGM cells did not affect DED progression. In conclusion, this study identifies the substance P-NK1R axis as a novel mechanism that reinforces the pathogenicity of ThGM cells in DED.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"101 1","pages":"e13434"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954239","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}

{"title":"Haematopoietic stem cell transplantation in children with inborn errors of immunity: A single centre experience.","authors":"Özlem Arman Bilir, Betül Karaatmaca, İkbal Ok Bozkaya, Şerife Mehtap Kanbur, Dilek Kaçar, Ayşe Metin, Namık Yaşar Özbek","doi":"10.1111/sji.13431","DOIUrl":"https://doi.org/10.1111/sji.13431","url":null,"abstract":"<p><p>This study retrospectively analyzed the outcomes of 61 pediatric patients with inborn errors of immunity (IEI) who underwent hematopoietic stem cell transplantation (HSCT) between 2011 and 2023. Patients were categorized into primary immunodeficiency disorders (PIDD), primary immune dysregulation disorders (PIRD), and congenital defects of phagocyte number or function (CDP). Median ages at diagnosis and HSCT were 9 and 30 months, respectively. With a median follow-up of 51 months, the overall survival (OS) was 70%, with a 100-day post-transplant OS of 80%. Transplant-related mortality (TRM) was 29%, with rates of 42%, 22.5%, and 27% for PIRD, PIDD, and CDP, respectively. This study highlights the importance of early diagnosis and HSCT in improving survival for IEI patients, while also emphasizing the need for continuous improvements in transplant protocols to minimize TRM and enhance quality of life.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":"101 1","pages":"e13431"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954237","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}

{"title":"Expression of STAT- and T-cell-related genes in women with first-line treatment of relapsing-remitting multiple sclerosis.","authors":"Ludmiła Szewczak, Maja Machcińska, Magdalena Kierasińska, Urszula Zawadzka-Więch, Marta Maruszewska-Cheruiyot, Paweł Majewski, Anna Karlińska, Rafał Rola, Katarzyna Donskow-Łysoniewska","doi":"10.1111/sji.13424","DOIUrl":"10.1111/sji.13424","url":null,"abstract":"<p><p>Relapsing-remitting multiple sclerosis is associated with changes in Jak/STAT pathways in immune cells, but the influence of disease-modifying drugs on these pathways is poorly understood. The aim of this study was to evaluate the impact of first-line disease-modifying drugs used in treatment of RRMS on expression of the STAT pathway and T-cell-related genes in the blood and on serum concentrations of sgp130 and TGF-β1 in women, as well as on the level of phosphorylated STAT3 and STAT5 proteins in T cells of untreated patients and heathy controls. Expression of STAT1, STAT3, STAT5A, STAT5B, SOCS1, SOCS3, FOXP3, IKZF2, RORC and ICOS genes in the blood of untreated RRMS patients, in the blood of patients treated with interferon-β, glatiramer acetate, dimethyl fumarate or teriflunomide and in the blood of healthy controls was evaluated using droplet digital PCR. Serum concentrations of sgp130 and TGF-β1 were evaluated by ELISA. Phosphorylated STAT3 and STAT5 protein levels in T cells were evaluated by flow cytometry. STAT3 gene expression was significantly higher in untreated patients than in healthy control, but the level of phosphorylated STAT3 in T cells was significantly lower. Patients treated with interferon-β or dimethyl fumarate had significantly lower STAT3 gene expression. Patients treated with teriflunomide had higher STAT1 gene expression, than untreated patients. Patients treated with dimethyl fumarate also had significantly lower RORC gene expression than untreated patients. The study shows the impact of drugs used in first-line treatment of relapsing-remitting multiple sclerosis on expression of STAT and T-cell-related genes.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13424"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639700","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}