Clinical & Translational Immunology最新文献

{"title":"Humoral and cellular immune responses in vaccinated and unvaccinated children following SARS-CoV-2 Omicron infection","authors":"Zheng Quan Toh,&nbsp;Jeremy Anderson,&nbsp;Nadia Mazarakis,&nbsp;Leanne Quah,&nbsp;Jill Nguyen,&nbsp;Rachel A Higgins,&nbsp;Lien Anh Ha Do,&nbsp;Yan Yung Ng,&nbsp;Sedi Jalali,&nbsp;Melanie R Neeland,&nbsp;Alissa McMinn,&nbsp;Richard Saffery,&nbsp;Sarah McNab,&nbsp;Jodie McVernon,&nbsp;Adrian Marcato,&nbsp;David P Burgner,&nbsp;Nigel Curtis,&nbsp;Andrew C Steer,&nbsp;Kim Mulholland,&nbsp;Daniel G Pellicci,&nbsp;Nigel W Crawford,&nbsp;Shidan Tosif,&nbsp;Paul V Licciardi","doi":"10.1002/cti2.70008","DOIUrl":"10.1002/cti2.70008","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The immune response in children elicited by SARS-CoV-2 Omicron infection alone or in combination with COVID-19 vaccination (hybrid immunity) is poorly understood. We examined the humoral and cellular immune response following SARS-CoV-2 Omicron infection in unvaccinated children and children who were previously vaccinated with COVID-19 mRNA vaccine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants were recruited as part of a household cohort study conducted during the Omicron predominant wave (Jan to July 2022) in Victoria, Australia. Blood samples were collected at 1, 3, 6 and 12 months following COVID-19 diagnosis. Humoral immune responses to SARS-CoV-2 Spike proteins from Wuhan, Omicron BA.1, BA.4/5 and JN.1, as well as cellular immune responses to Wuhan and BA.1 were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 43 children and 113 samples were included in the analysis. Following Omicron infection, unvaccinated children generated low antibody responses but elicited Spike-specific CD4 and CD8 T-cell responses. In contrast, vaccinated children infected with the Omicron variant mounted robust humoral and cellular immune responses to both ancestral strain and Omicron subvariants. Hybrid immunity persisted for at least 6 months post infection, with cellular immune memory characterised by the generation of Spike-specific polyfunctional CD8 T-cell responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SARS-CoV-2 hybrid immunity in children is characterised by persisting SARS-CoV-2 antibodies and robust CD4 and CD8 T-cell activation and polyfunctional responses. Our findings contribute to understanding hybrid immunity in children and may have implications regarding COVID-19 vaccination and SARS-CoV-2 re-infections.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-15-induced CD38+HLA-DR+CD8+ T cells correlate with liver injury via NKG2D in chronic hepatitis B cirrhosis","authors":"Jing Fan,&nbsp;Min Xu,&nbsp;Ke Liu,&nbsp;Wanping Yan,&nbsp;Huanyu Wu,&nbsp;Hongliang Dong,&nbsp;Yongfeng Yang,&nbsp;Wei Ye","doi":"10.1002/cti2.70007","DOIUrl":"https://doi.org/10.1002/cti2.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>CD8⁺ T cells play a critical role in the immune dysfunction associated with liver cirrhosis. CD38⁺HLA-DR⁺CD8⁺ T cells, or bystander-activated CD8⁺ T cells, are involved in tissue injury but their specific contribution to liver cirrhosis remains unclear. This study sought to identify the mechanism for CD38⁺HLA-DR⁺CD8⁺ T cell-mediated pathogenesis during liver cirrhosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The immunophenotype, antigen specificity, cytokine secretion and cytotoxicity-related indicators of CD38⁺HLA-DR⁺CD8⁺ T cells were determined using flow cytometry. The functional properties of these cells were assessed using transcriptome analysis. CD38⁺HLA-DR⁺CD8⁺ T-cell killing was detected using cytotoxicity and antibody-blocking assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The proportion of CD38⁺HLA-DR⁺CD8⁺ T cells was significantly elevated in liver cirrhosis patients and correlated with tissue damage. Transcriptome analysis revealed that these cells had innate-like functional characteristics. This CD8⁺ T-cell population primarily consisted of effector memory T cells and produced a high level of cytotoxicity-related cytokines, granzyme B and perforin. IL-15 promoted CD38⁺HLA-DR⁺CD8⁺ T-cell activation and proliferation, inducing significant TCR-independent cytotoxicity mediated through NKG2D.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CD38⁺HLA-DR⁺CD8⁺ T cells correlated with cirrhosis-related liver injury and contributed to liver damage by signalling through NKG2D in a TCR-independent manner.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142404496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of PD-1+CD4+ T cells in peripheral blood and synovium of rheumatoid arthritis patients","authors":"Yan-juan Chen,&nbsp;Yong Chen,&nbsp;Ping Chen,&nbsp;Yi-qun Jia,&nbsp;Hua Wang,&nbsp;Xiao-ping Hong","doi":"10.1002/cti2.70006","DOIUrl":"https://doi.org/10.1002/cti2.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>PD-1 plays a crucial role in the immune dysregulation of rheumatoid arthritis (RA), but the specific characteristics of PD-1⁺CD4⁺ T cells remain unclear and require further investigation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Circulating PD-1⁺CD4⁺ T cells from RA patients were analysed using flow cytometry. Plasma levels of soluble PD-1 (sPD-1) were measured using enzyme-linked immunosorbent assay (ELISA). Single-cell RNA sequence data from peripheral blood mononuclear cells (PBMCs) and synovial tissue of patients were obtained from the GEO and the ImmPort databases. Bioinformatics analyses were performed in the R studio to characterise PD-1⁺CD4⁺ T cells. Expression of CCR7, KLF2 and IL32 in PD-1⁺CD4⁺ T cells was validated by flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>RA patients showed an elevated proportion of PD-1⁺CD4⁺ T cells in peripheral blood, along with increased plasma sPD-1 levels, which positively correlated with TNF-α and erythrocyte sedimentation rate. Bioinformatic analysis revealed <i>PD-1</i> expression on CCR7⁺CD4⁺ T cells in PBMCs, and on both CCR7⁺CD4⁺ T cells and CXCL13⁺CD4⁺ T cells in RA synovium. PD-1 was co-expressed with CCR7, KLF2, and IL32 in peripheral CD4⁺ T cells. In synovium, PD-1⁺CCR7⁺CD4⁺ T cells had higher expression of <i>TNF</i> and <i>LCP2</i>, while PD-1⁺CXCL13⁺CD4⁺ T cells showed elevated levels of <i>ARID5A</i> and <i>DUSP2</i>. PD-1⁺CD4⁺ T cells in synovium also appeared to interact with B cells and fibroblasts through BTLA and TNFSF signalling pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study highlights the increased proportion of PD-1⁺CD4⁺ T cells and elevated sPD-1 levels in RA. The transcriptomic profiles and signalling networks of PD-1⁺CD4⁺ T cells offer new insights into their role in RA pathogenesis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 10","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cord blood granulocyte levels are associated with severe bronchiolitis in the first year of life","authors":"Gabriela Martins Costa Gomes,&nbsp;Carla Rebeca Da Silva Sena,&nbsp;Vanessa E Murphy,&nbsp;Philip M Hansbro,&nbsp;Malcolm R Starkey,&nbsp;Peter G Gibson,&nbsp;Joerg Mattes,&nbsp;Adam M Collison","doi":"10.1002/cti2.70004","DOIUrl":"https://doi.org/10.1002/cti2.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Bronchiolitis is a leading cause of infant hospitalisation in the first year of life, and it preferentially affects infants born to mothers with asthma. Here, we evaluate cord blood granulocytes in infants born to mothers with asthma participating in the Breathing for Life Trial (BLT), to investigate early life determinants of bronchiolitis hospitalisation within the first year of life.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cord blood from 89 participants was collected into EDTA tubes and processed within 6 h of birth. Cells were stained in whole cord blood for eosinophils (CD45⁺, CD193⁺, CD16⁻), and neutrophils (CD45⁺, CD193⁻, CD16⁺). Medical records were reviewed for bronchiolitis hospitalisation in the first 12 months of life. Statistical analyses were conducted using Stata IC16.1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Logistic regression adjusted for caesarean section, gestational age, maternal smoking during pregnancy, foetal heart deceleration during labour, and season of birth revealed an association between cord blood eosinophil levels and bronchiolitis hospitalisation in the first 12 months of life with an Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve of 0.943 (aOR = 1.35, <i>P</i> = 0.011). Neutrophils were associated with the risk of bronchiolitis hospitalisation in a univariable logistic regression (OR = 0.93, <i>P</i> = 0.029); however, there was no statistical significance in the adjusted model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Higher eosinophil numbers in cord blood were associated with bronchiolitis hospitalisation in the first 12 months in a cohort of infants born to asthmatic mothers. This suggests that susceptibility to bronchiolitis in later life is influenced by the immune cell profile prior to viral infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulmonary complications post allogeneic haematopoietic stem cell transplant in children","authors":"Hannah Walker,&nbsp;Joanne Abbotsford,&nbsp;Gabrielle M Haeusler,&nbsp;Daniel Yeoh,&nbsp;Shanti Ramachandran,&nbsp;Michelle Ng,&nbsp;Jonathan Holzmann,&nbsp;Shivanthan Shanthikumar,&nbsp;Heather Weerdenburg,&nbsp;Diane Hanna,&nbsp;Melanie R Neeland,&nbsp;Theresa Cole","doi":"10.1002/cti2.70003","DOIUrl":"https://doi.org/10.1002/cti2.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Haematopoietic stem cell transplant (HCT) is a cellular therapy that, whilst curative for a child's underlying disease, carries significant risk of mortality, including because of pulmonary complications. The aims of this study were to describe the burden of pulmonary complications post-HCT in a cohort of Australian children and identify risk factors for the development of these complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients were identified from the HCT databases at two paediatric transplant centres in Australia. Medical records were reviewed, and demographics, HCT characteristics and pulmonary complications documented. Relative risk ratio was used to identify risk factors for developing pulmonary complications prior to first transplant episode, and survival analysis performed to determine hazard ratio.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 243 children underwent transplant during the study period, and pulmonary complications occurred in 48% (117/243) of children. Infectious complications were more common (55%) than non-infective complications (18%) and 26% of patients developed both. Risk factors for the development of pulmonary complications included the following: diagnoses of MPAL (RR 2.16, <i>P</i> = 0.02), matched unrelated donor (RR1.34, <i>P</i> = 0.03), peripheral blood (RR 1.36, <i>P</i> = 0.028) or cord blood (RR 1.73, <i>P</i> = 0.012) as the stem cell source and pre-existing lung disease (RR1.72, <i>P</i> &lt; 0.0001). Children with a post-HCT lung complication had a significantly increased risk of mortality compared with those who did not (HR 3.9, <i>P</i> &lt; 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates pulmonary complications continue to occur frequently in children post-HCT and contribute significantly to mortality. Highlighting the need for improved strategies to identify patients at risk pre-transplant and enhanced treatments for those who develop lung disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers to predict and diagnose pulmonary complications in children post haematopoietic stem cell transplant","authors":"Hannah Walker,&nbsp;Gabrielle M Haeusler,&nbsp;Theresa Cole,&nbsp;Melanie Neeland,&nbsp;Diane Hanna,&nbsp;Shivanthan Shanthikumar","doi":"10.1002/cti2.70002","DOIUrl":"https://doi.org/10.1002/cti2.70002","url":null,"abstract":"<p>Objectives. Haematopoietic cell transplant (HCT) is a cellular therapy for a group of high-risk children with cancer, immunodeficiency and metabolic disorders. Whilst curative for a child's underlying condition, HCT has significant risks associated, including lung injury. These complications are associated with increased post HCT mortality and require improved methods of risk stratification, diagnosis and treatment. Methods. Biomarkers measured in bronchoalveolar fluid and peripheral blood have been identified for both acute and chronic lung injury post HCT.This review evaluates the current research available investigating the use of these biomarkers to improve clinical care, with a focus on the paediatric cohort. Results. Elevated levels of cytokines such as IL-6, IL-8, G-CSF and TNF were identified as potential predictive biomarkers for the development of post HCT lung disease. The pulmonary microbiome was found to have strong potential as a biomarker pre and post HCT for the development of pulmonary complications. General limitations of the studies identified were study design, retrospective or single centre and not exclusively performed in the paediatric population. Conclusion. To translate biomarker discovery into clinical implementation further research is required, utilising larger cohorts of children in prospective trials to validate these biomarkers and determine how they can be translated into better outcomes for children post HCT.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Omega-6 Lipid pathway shift is associated with neutrophil influx and structural lung damage in early cystic fibrosis lung disease","authors":"Lisa JM Slimmen,&nbsp;Jelle Y Broos,&nbsp;Badies HAN Manaï,&nbsp;Silvia C Estevão,&nbsp;Martin Giera,&nbsp;Gijs Kooij,&nbsp;Wendy WJ Unger,&nbsp;Hettie M Janssens","doi":"10.1002/cti2.70000","DOIUrl":"https://doi.org/10.1002/cti2.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>In cystic fibrosis (CF), an imbalanced lipid metabolism is associated with lung inflammation. Little is known about the role that specific lipid mediators (LMs) exert in CF lung inflammation, and whether their levels change during early disease progression. Therefore, we measured airway LM profiles of young CF patients, correlating these with disease-associated parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Levels of omega (ω)-3/6 PUFAs and their LM derivatives were determined in bronchoalveolar lavage fluid (BALF) of children with CF ages 1–5 using a targeted high-performance liquid chromatography–tandem mass spectrometry approach. Hierarchical clustering analysis was performed on relative LM levels. Individual relative LM levels were correlated with neutrophilic inflammation (BALF %Neu) and structural lung damage (PRAGMA-CF %Disease). Significant correlations were included in a backward multivariate linear regression model to identify the LMs that are best related to disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 65 BALF samples were analysed for ω-3/6 lipid content. LM profiles clustered into an arachidonic acid (AA)-enriched and a linoleic acid (LA)-enriched sample cluster. AA derivatives like 17-OH-DH-HETE, 5-HETE, 5,15-diHETE, 15-HETE, 15-KETE, LTB₄ and 6-trans-LTB₄ positively correlated with BALF %Neu and/or PRAGMA %Dis. Contrastingly, 9-HoTrE and the LA derivatives 9-HoDE, 9(10)-EpOME, 9(10)-DiHOME, 13-HoDE, 13-oxoODE and 12(13)-EpOME negatively correlated with BALF %Neu and/or PRAGMA %Dis. 6-trans-LTB₄ was the strongest predictor for BALF %Neu. 5-HETE and 15-KETE contributed most to PRAGMA %Dis prediction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data provide more insight into the lung lipidome of infants with CF, and show that a shift from LA derivatives to AA derivatives in BALF associates with early CF lung disease progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Siglec-7 and Siglec-9 expression in primary triple negative and oestrogen receptor positive breast cancer and in vitro signalling","authors":"Eline JH van Houtum,&nbsp;Anne HC Valk,&nbsp;Daniel Granado,&nbsp;Jasper Lok,&nbsp;Lune van den Bogaard,&nbsp;Naomi Remkes,&nbsp;Jesper van Eck van der Sluijs,&nbsp;Paul N Span,&nbsp;Lenneke AM Cornelissen,&nbsp;Gosse J Adema","doi":"10.1002/cti2.1524","DOIUrl":"https://doi.org/10.1002/cti2.1524","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>PD-1/PD-L1 immune checkpoint blockade can be an effective treatment for advanced breast cancer patients. However, patients with oestrogen receptor positive (ER+) tumors often display only low lymphocyte infiltration, while a large part of triple negative (TN) breast tumors does not generate an effective immunotherapy response. Therefore, new treatment strategies have to be developed. Here, we investigate Siglec-7 and Siglec-9 as novel ITIM-bearing inhibitory immune checkpoint receptors similar to PD-1, but expressed on a broader range of immune cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed Siglec-7 and Siglec-9 (ligand) expression in TN and ER+ breast cancer tumors and their breast cancer cell line-induced signalling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We report that Siglec-7 and Siglec-9 are highly expressed in TN tumors, and to a low extent in ER+ tumors. Siglec-7 was observed on myeloid cells, T cells, and NK cells and Siglec-9 preferentially on myeloid cells. Expression of sialoglycans, including Siglec-7 and Siglec-9 ligands, was observed in both TN and ER+ breast cancer tissue sections. Expression levels of Siglec-7 and Siglec-9 ligands were higher on <i>in vitro</i> cultured TN cell lines than ER+ cell lines. Importantly, by applying chimeric Siglec-7 reporter cells, we showed the induction of Siglec-7 signalling by multiple TN cell lines, but only by one ER+ cell line. Moreover, Siglec-7 signalling is directly related to Siglec-7 ligand expression levels of breast cancer cell lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These data imply that immunotherapy targeting Siglec receptors may be particularly interesting for TN breast cancer patients not responding to current treatment strategies with tumors displaying high immune cell infiltration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1524","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Schistosoma excretory/secretory products: an untapped library of tolerogenic immunotherapeutics against food allergy","authors":"Madeleine Rogers,&nbsp;Sandip Kamath,&nbsp;Donald McManus,&nbsp;Malcolm Jones,&nbsp;Catherine Gordon,&nbsp;Severine Navarro","doi":"10.1002/cti2.70001","DOIUrl":"https://doi.org/10.1002/cti2.70001","url":null,"abstract":"<p>Food allergy (FA) is considered the ‘second wave’ of the allergy epidemic in developed countries after asthma and allergic rhinitis with a steadily growing burden of 40%. The absence of early childhood pathogen stimulation embodied by the hygiene hypothesis is one explanation, and in particular, the eradication of parasitic helminths could be at play. Infections with parasites <i>Schistosoma</i> spp. have been found to have a negative correlation with allergic diseases. Schistosomes induce regulatory responses to evade immune detection and ensure their long-term survival. This is achieved via excretory/secretory (E/S) products, consisting of proteins, lipids, metabolites, nucleic acids and extracellular vesicles, representing an untapped therapeutic avenue for the treatment of FA without the unpleasant side-effects and risks associated with live infection. Schistosome-derived immunotherapeutic development is in its infancy and novel discoveries are heavily technology dependent; thus, it is essential to better understand how newly identified molecules interact with host immune systems to ensure safety and successful translation. This review will outline the identified <i>Schistosoma</i>-derived E/S products at all life cycle stages and discuss known mechanisms of action and their ability to suppress FA.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 9","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-signal recognition particle antibodies induce cardiac diastolic dysfunction via oxidative stress injury","authors":"Hao Zhang,&nbsp;Yunjing Shi,&nbsp;Yingze Fan,&nbsp;Dehao Zhu,&nbsp;Zeping Qiu,&nbsp;Huihui Chi,&nbsp;Qiongyi Hu,&nbsp;Liangzhe Xie,&nbsp;Yue Sun,&nbsp;Honglei Liu,&nbsp;Xiaobing Cheng,&nbsp;Junna Ye,&nbsp;Hui Shi,&nbsp;Zhuochao Zhou,&nbsp;Jianfen Meng,&nbsp;Jialin Teng,&nbsp;Chengde Yang,&nbsp;Wei Jin,&nbsp;Yutong Su","doi":"10.1002/cti2.1525","DOIUrl":"https://doi.org/10.1002/cti2.1525","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Anti-signal recognition particle (SRP) antibodies, markers of immune-mediated necrotising myopathy, are reportedly related to cardiac involvement; however, whether they are pathogenic to the myocardium remains unclear. We aimed, therefore, to explore the pathogenicity of anti-SRP antibodies against the myocardium through <i>in vivo</i> and <i>in vitro</i> studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Total immunoglobulin G (IgG), purified from patients with positive anti-SRP antibodies, was passively transferred into C57BL/6 mice. Cardiac function was evaluated via echocardiography and the ventricular pressure–volume loop; cardiac histological changes were analysed using haematoxylin–eosin staining, picrosirius red staining, immunofluorescence and immunohistochemistry. Additionally, reactive oxygen species (ROS) formation was evaluated by dihydroethidium (DHE) staining; mitochondrial morphology and function were evaluated using transmission electron microscopy and seahorse mitochondrial respiration assay, respectively. The myositis cohort at our centre was subsequently reviewed in terms of cardiac assessments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After the passive transfer of total IgG from patients with positive anti-SRP antibodies, C57BL/6 mice developed significant left ventricular diastolic dysfunction (LVDD). Transcriptomic analysis and corresponding experiments revealed increased oxidative stress and mitochondrial damage in the hearts of the experimental mice. Cardiomyocytes exposed to anti-SRP-specific IgG, however, recovered normal mitochondrial metabolism after treatment with N-acetylcysteine, an ROS scavenger. Moreover, patients positive for anti-SRP antibodies manifested worse diastolic but equivalent systolic function compared to their counterparts after propensity score matching.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Anti-SRP antibodies may play a pathogenic role in the development of LVDD by promoting ROS production and subsequent myocardial mitochondrial impairment. The inhibition of oxidative stress was effective in reversing anti-SRP antibody-induced LVDD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 8","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1525","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141973634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}