{"title":"Central Tolerance or Central Adaptation?","authors":"Masoud H Manjili","doi":"10.1111/sji.70011","DOIUrl":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matyas Meggyes, David U Nagy, Ildiko Toth, Timoteus Feik, Beata Polgar, Iyad Saad Al Deen, David Sipos, Laszlo Szereday, Agnes Peterfalvi
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.
{"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}
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
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.
与自体妊娠相比,卵母细胞捐献(OD)妊娠显示出更高的胎儿-母体不相容性和患先兆子痫(PE)的风险。由于母体单核细胞在异体胎儿的耐受性中起作用,本研究旨在分析健康妊娠和子痫前期 OD 妊娠的单核细胞表型。我们在不同的妊娠时间点采集了健康(10 例)和 PE(5 例)外周妊娠的母体外周血。计算胎儿与母体人类白细胞抗原(HLA)的错配情况。我们使用极光光谱流式细胞术的 35 色抗体面板来分析单核细胞亚群的组成和表面标志物的表达。在健康 OD 孕妇的整个妊娠期,中间单核细胞上 CD38 的表达明显增加。与健康组相比,PE 组单核细胞亚群的 CD38 表达量更高,具有统计学意义。免疫抑制受体 CD85j(LILRB1)和 CD85d(LILRB2)以及单核细胞募集调节分子 CCR2 和 CD91 在 PE 期间在单核细胞亚群上的表达也明显增加。如果仅在 HLA 高度不匹配的妊娠中比较健康和 PE OD,CD38 和 CD85j 在单核细胞亚群中的表达差异仍然显著。总之,在健康的外周妊娠中,CD38表达的上调可能反映了妊娠三个月时的促炎症状态。在 PE OD 妊娠中,母体外周单核细胞亚群中炎症和免疫调节标志物的表达都会增加。这些亚群中 CCR2 和 CD91 表达的升高可能反映了单核细胞的趋化作用以及 PE 晚期全身血管功能障碍的影响。
{"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}
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.
{"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}
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
{"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}
Tiana Stanisic, Emma Uttrup Ewing, Alma Lindell, Fatima Al-Jaberi, Martin Kongsbak-Wismann
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 (TH)1 and TH2 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 TH1/TH2 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.
{"title":"Vitamin D<sub>3</sub>-VDR and vitamin A-RAR affect IL-13 and IFNγ secretion from human CD4<sup>+</sup> 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":"https://doi.org/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 D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) and 9-cis retinoic acid (9cRA) on T helper (T<sub>H</sub>)1 and T<sub>H</sub>2 cytokines and transcription factors in primary human blood-derived CD4<sup>+</sup> 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)<sub>2</sub>D<sub>3</sub> upregulated IL-13 and suppressed IFNγ, while 9cRA had the opposite effects. This was largely independent of a T<sub>H</sub>1/T<sub>H</sub>2 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)<sub>2</sub>D<sub>3</sub> 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)<sub>2</sub>D<sub>3</sub> 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)<sub>2</sub>D<sub>3</sub> 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}
Özlem Arman Bilir, Betül Karaatmaca, İkbal Ok Bozkaya, Şerife Mehtap Kanbur, Dilek Kaçar, Ayşe Metin, Namık Yaşar Özbek
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.
{"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}
Hua Rong, Hai Yang, Qingqing Liu, Hui Zhang, Shaolin Wang
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.
{"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<sup>+</sup> T cells play a significant role in its pathogenesis. A CD4<sup>+</sup> 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}
Pub Date : 2025-01-01Epub Date: 2024-11-15DOI: 10.1111/sji.13424
Ludmiła Szewczak, Maja Machcińska, Magdalena Kierasińska, Urszula Zawadzka-Więch, Marta Maruszewska-Cheruiyot, Paweł Majewski, Anna Karlińska, Rafał Rola, Katarzyna Donskow-Łysoniewska
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.
复发性多发性硬化症与免疫细胞中Jak/STAT通路的变化有关,但人们对疾病调节药物对这些通路的影响知之甚少。本研究的目的是评估用于治疗 RRMS 的一线疾病调节药物对血液中 STAT 通路和 T 细胞相关基因的表达、女性血清中 sgp130 和 TGF-β1 浓度的影响,以及对未经治疗的患者和健康对照组 T 细胞中磷酸化 STAT3 和 STAT5 蛋白水平的影响。使用液滴数字 PCR 评估了未经治疗的 RRMS 患者血液中、接受干扰素-β、醋酸格拉替雷、富马酸二甲酯或特氟隆胺治疗的患者血液中以及健康对照组血液中 STAT1、STAT3、STAT5A、STAT5B、SOCS1、SOCS3、FOXP3、IKZF2、RORC 和 ICOS 基因的表达情况。血清中 sgp130 和 TGF-β1 的浓度通过 ELISA 进行评估。流式细胞术评估了 T 细胞中磷酸化 STAT3 和 STAT5 蛋白水平。未经治疗的患者 STAT3 基因表达明显高于健康对照组,但 T 细胞中磷酸化 STAT3 的水平明显低于健康对照组。接受干扰素-β或富马酸二甲酯治疗的患者的STAT3基因表达量明显较低。与未接受治疗的患者相比,接受特立氟胺治疗的患者 STAT1 基因表达较高。接受富马酸二甲酯治疗的患者的 RORC 基因表达也明显低于未接受治疗的患者。这项研究显示了用于复发性多发性硬化症一线治疗的药物对 STAT 和 T 细胞相关基因表达的影响。
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Pub Date : 2025-01-01Epub Date: 2024-11-19DOI: 10.1111/sji.13419
Yan Feng, Zhishou Zhang, Hui Huangfu, Haiyang Han, Bailing Xie, Shuo Song, Tao Liu, Yunfang An, Pingchang Yang
Allergen-specific immunotherapy (AIT) is an aetiology-targeting therapy for allergic diseases. The therapeutic mechanism of AIT is not fully understood yet. Endoplasmic reticulum stress is associated with the pathogenesis of allergic disorders. This study aims to elucidate the effects of AIT on suppressing allergic response through regulating endoplasmic reticulum stress. In this study, patients with perennial allergic rhinitis were recruited. AIT was conducted for the patients. An allergic rhinitis (AR) mouse model was established with mite extracts as allergens. We found that AIT modulated the endoplasmic reticulum stress status in peripheral CD4+ T cells in patients with allergic rhinitis. The intensity of endoplasmic reticulum stress associated the PERK (protein kinase RNA-like endoplasmic reticulum kinase)-eIF2a (eukaryotic translation initiation factor 2a) axis in CD4+ T cells was upregulated by AIT, which was closely associated with the improvement in allergic rhinitis response after AIT. eIF2a interacted with GATA3 to downregulate the IL4 gene transcription in CD4+ T cells. High doses of aluminium hydroxide (alum) in AIT vaccines enhanced the activity of XBP1 to suppress eIF2a in CD4+ T cells. AIT containing a low dose of alum effectively mitigated the experimental allergic rhinitis, while the AIT without alum or a high dose of alum exacerbated the experimental allergic rhinitis. In conclusion, the alum adjuvant in allergen vaccines can regulate the activity of eIF2a to regulate the expression of Th2 cytokines in CD4+ T cells. Manipulating the alum dose in AIT vaccines has the potential to enhance the therapeutic effects of AIT.
过敏原特异性免疫疗法(AIT)是一种针对过敏性疾病的病原学疗法。过敏原特异性免疫疗法的治疗机制尚未完全明了。内质网应激与过敏性疾病的发病机制有关。本研究旨在阐明 AIT 通过调节内质网应激抑制过敏反应的作用。本研究招募了常年过敏性鼻炎患者。对患者进行了 AIT 治疗。以螨虫提取物为过敏原,建立了过敏性鼻炎(AR)小鼠模型。我们发现,AIT 可调节过敏性鼻炎患者外周 CD4+ T 细胞的内质网应激状态。AIT 上调了 CD4+ T 细胞中与 PERK(蛋白激酶 RNA 样内质网激酶)-eIF2a(真核翻译起始因子 2a)轴相关的内质网应激强度,这与 AIT 后过敏性鼻炎反应的改善密切相关。AIT 疫苗中的高剂量氢氧化铝(明矾)增强了 XBP1 抑制 CD4+ T 细胞中 eIF2a 的活性。含有低剂量明矾的 AIT 能有效缓解实验性过敏性鼻炎,而不含明矾或高剂量明矾的 AIT 则会加重实验性过敏性鼻炎。总之,过敏原疫苗中的明矾佐剂可以调节 eIF2a 的活性,从而调节 CD4+ T 细胞中 Th2 细胞因子的表达。调节过敏原疫苗中明矾的剂量有可能增强过敏原疫苗的治疗效果。
{"title":"Adjuvant alum regulates the eIF2a-GATA3 axis in CD4<sup>+</sup> T cells to influence allergen immunotherapy.","authors":"Yan Feng, Zhishou Zhang, Hui Huangfu, Haiyang Han, Bailing Xie, Shuo Song, Tao Liu, Yunfang An, Pingchang Yang","doi":"10.1111/sji.13419","DOIUrl":"10.1111/sji.13419","url":null,"abstract":"<p><p>Allergen-specific immunotherapy (AIT) is an aetiology-targeting therapy for allergic diseases. The therapeutic mechanism of AIT is not fully understood yet. Endoplasmic reticulum stress is associated with the pathogenesis of allergic disorders. This study aims to elucidate the effects of AIT on suppressing allergic response through regulating endoplasmic reticulum stress. In this study, patients with perennial allergic rhinitis were recruited. AIT was conducted for the patients. An allergic rhinitis (AR) mouse model was established with mite extracts as allergens. We found that AIT modulated the endoplasmic reticulum stress status in peripheral CD4<sup>+</sup> T cells in patients with allergic rhinitis. The intensity of endoplasmic reticulum stress associated the PERK (protein kinase RNA-like endoplasmic reticulum kinase)-eIF2a (eukaryotic translation initiation factor 2a) axis in CD4<sup>+</sup> T cells was upregulated by AIT, which was closely associated with the improvement in allergic rhinitis response after AIT. eIF2a interacted with GATA3 to downregulate the IL4 gene transcription in CD4<sup>+</sup> T cells. High doses of aluminium hydroxide (alum) in AIT vaccines enhanced the activity of XBP1 to suppress eIF2a in CD4<sup>+</sup> T cells. AIT containing a low dose of alum effectively mitigated the experimental allergic rhinitis, while the AIT without alum or a high dose of alum exacerbated the experimental allergic rhinitis. In conclusion, the alum adjuvant in allergen vaccines can regulate the activity of eIF2a to regulate the expression of Th2 cytokines in CD4<sup>+</sup> T cells. Manipulating the alum dose in AIT vaccines has the potential to enhance the therapeutic effects of AIT.</p>","PeriodicalId":21493,"journal":{"name":"Scandinavian Journal of Immunology","volume":" ","pages":"e13419"},"PeriodicalIF":4.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676786","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}