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Reduced EO771-induced tumour growth and increased overall-survival of mice ablated for immune cell-specific catalytic subunit Cβ2 of protein kinase A 消减免疫细胞特异性蛋白激酶 A 催化亚基 Cβ2 的小鼠可减少 EO771 诱导的肿瘤生长并提高总体存活率。
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-06-20 DOI: 10.1016/j.imlet.2024.106884
Shuai Guo , Shrikant Kolan , Gaoyang Li , Clara Louise Hammarström , Franco Grimolizzi , Linda Elin Birkhaug Stuhr , Bjørn Steen Skålhegg
{"title":"Reduced EO771-induced tumour growth and increased overall-survival of mice ablated for immune cell-specific catalytic subunit Cβ2 of protein kinase A","authors":"Shuai Guo ,&nbsp;Shrikant Kolan ,&nbsp;Gaoyang Li ,&nbsp;Clara Louise Hammarström ,&nbsp;Franco Grimolizzi ,&nbsp;Linda Elin Birkhaug Stuhr ,&nbsp;Bjørn Steen Skålhegg","doi":"10.1016/j.imlet.2024.106884","DOIUrl":"10.1016/j.imlet.2024.106884","url":null,"abstract":"<div><p>Ablation of the immune-specific catalytic subunit Cβ2 of protein kinase A is associated with a proinflammatory phenotype and increased sensitivity to autoimmunity in mice. Here we show that tumour growth of the adenocarcinoma cell line EO771 in the breast and in the lung after injection into the mammary fat pad and tail vein, respectively, was significantly reduced in mice ablated for Cβ2 compared to wild-type mice. In both cases, the breast and lung tumours showed increased infiltration of immune cells in the mice lacking Cβ2 compared to wild-type mice. Despite this, it appeared that solid tissue- versus intravenously injected EO771 cells evoked different immune responses. This was reflected by significantly increased levels of splenic proinflammatory immune cells and circulating cytokines in Cβ2 ablated mice carrying breast- but not the lung tumours. Moreover, Cβ2 ablated mice injected with EO771 cells showed increased overall survival compared to wild-type mice. Taken together, our results suggest for a role for immune cell-specific Cβ2 in protecting against tumour growth induced by EO771 cells in mice that is reflected in improved overall survival.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000580/pdfft?md5=ed9927c067b97bdfc75f18e01490ff46&pid=1-s2.0-S0165247824000580-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440448","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}
引用次数: 0
Effect of antimetabolite regimen on cellular and humoral immune response to SARS-COV-2 vaccination in solid organ transplant recipients 抗代谢药方案对实体器官移植受者接种SARS-COV-2疫苗后细胞和体液免疫反应的影响
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-06-19 DOI: 10.1016/j.imlet.2024.106886
Manuela Capone , Anna Vanni , Lorenzo Salvati , Giulia Lamacchia , Alessio Mazzoni , Laura Maggi , Lorenzo Cosmi , Francesco Liotta , Paola Romagnani , Luigi Cirillo , Elisa Buti , Vito Terlizzi , Chiara Azzari , Francesco Citera , Federica Barbati , Gian Maria Rossolini , Silvia Bresci , Beatrice Borchi , Annalisa Cavallo , Jessica Mencarini , Francesco Annunziato
{"title":"Effect of antimetabolite regimen on cellular and humoral immune response to SARS-COV-2 vaccination in solid organ transplant recipients","authors":"Manuela Capone ,&nbsp;Anna Vanni ,&nbsp;Lorenzo Salvati ,&nbsp;Giulia Lamacchia ,&nbsp;Alessio Mazzoni ,&nbsp;Laura Maggi ,&nbsp;Lorenzo Cosmi ,&nbsp;Francesco Liotta ,&nbsp;Paola Romagnani ,&nbsp;Luigi Cirillo ,&nbsp;Elisa Buti ,&nbsp;Vito Terlizzi ,&nbsp;Chiara Azzari ,&nbsp;Francesco Citera ,&nbsp;Federica Barbati ,&nbsp;Gian Maria Rossolini ,&nbsp;Silvia Bresci ,&nbsp;Beatrice Borchi ,&nbsp;Annalisa Cavallo ,&nbsp;Jessica Mencarini ,&nbsp;Francesco Annunziato","doi":"10.1016/j.imlet.2024.106886","DOIUrl":"10.1016/j.imlet.2024.106886","url":null,"abstract":"<div><h3>Objective</h3><p>Novel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2 protecting individuals, especially the immunocompromised, from COVID-19. Still, it remains largely unknown how solid organ transplant and different immunosuppressive medications affect development of vaccine-induced immunity.</p></div><div><h3>Methods</h3><p>In this work, we monitored humoral and cellular memory responses after mRNA SARS-CoV-2 two-doses and booster doses vaccination in cystic fibrosis lung transplanted patients (CFT) and compared them with both cystic fibrosis patients without lung transplant (CF) and with kidney transplant recipients (KT). In particular, we investigated the effects of immunosuppressive regimens on immune memory to SARS-CoV-2 after mRNA SARS-CoV-2 vaccine in transplanted patients.</p></div><div><h3>Results</h3><p>Our results showed that immunocompromised transplanted patients displayed a weak cellular and humoral memory to SARS-CoV-2 mRNA vaccination. In addition, obtained data clearly demonstrate that immunosuppressive therapy regimen including antimetabolites, further reduces patients’ ability to respond to vaccination at both humoral and cell-mediated level. Notably, patient treated with antimetabolites showed a lower humoral and cellular response also after a booster dose vaccination.</p></div><div><h3>Conclusion</h3><p>These results, even if obtained on a small patient's cohort, question whether immunocompromised patients need interventions to improve vaccine SARS-CoV-2 mRNA vaccine response such as additional jab or modulation of immunosuppressive therapy.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436851","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}
引用次数: 0
Differential structure and immunomodulatory functions of lipophosphoglycan between Leishmania spp 利什曼原虫脂磷聚糖的结构和免疫调节功能差异
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-06-18 DOI: 10.1016/j.imlet.2024.106885
Lisa U. Teufel, Leo A.B. Joosten, Jéssica C. dos Santos
{"title":"Differential structure and immunomodulatory functions of lipophosphoglycan between Leishmania spp","authors":"Lisa U. Teufel,&nbsp;Leo A.B. Joosten,&nbsp;Jéssica C. dos Santos","doi":"10.1016/j.imlet.2024.106885","DOIUrl":"10.1016/j.imlet.2024.106885","url":null,"abstract":"<div><p>Leishmaniasis is a collective term for several tropical, neglected diseases caused by protozoans of the species <em>Leishmania</em>, 20 of which causing disease in humans ranging from localised self-healing lesions to chronic manifestations which affect the skin or inner organs. Although millions of infections are accounted for annually, treatment options are scarce and limited to medication associated with heavy side-effects and increasing antibiotic resistance. Case studies point towards immunotherapy as effective alternative treatment relying on immunomodulatory properties of e.g., the Bacillus Calmette-Guérin vaccine. <em>Leishmania</em> parasites are also known to modulate the immune system, yet the underlying macromolecules and surface molecules remain widely under characterised. With this short review, we aim to provide a complete summary of the existing literature describing one of the most expressed surface molecule on <em>Leishmania</em> spp, lipophosphoglycan (LPG), which shows great variability between different lifecycle stages and different <em>Leishmania</em> spp. Complete characterisation of LPG may aid to improve treatment and aid the development of vaccination strategies, and open new avenues to exploit the immunomodulatory properties of LPG in unrelated conditions.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000592/pdfft?md5=365d7974acaf4c75e767330b92c744f2&pid=1-s2.0-S0165247824000592-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431818","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}
引用次数: 0
Gut dysbiosis impacts the immune system and promotes prostate cancer 肠道菌群失调会影响免疫系统,诱发前列腺癌。
IF 4.4 4区 医学
Immunology letters Pub Date : 2024-06-08 DOI: 10.1016/j.imlet.2024.106883
Ritis K. Shyanti , Jazmyn Greggs , Shalie Malik , Manoj Mishra
{"title":"Gut dysbiosis impacts the immune system and promotes prostate cancer","authors":"Ritis K. Shyanti ,&nbsp;Jazmyn Greggs ,&nbsp;Shalie Malik ,&nbsp;Manoj Mishra","doi":"10.1016/j.imlet.2024.106883","DOIUrl":"10.1016/j.imlet.2024.106883","url":null,"abstract":"<div><p>The gut microbiota is a system of microorganisms in the human gastrointestinal (GI) system, consisting of trillions of microorganisms residing in epithelial surfaces of the body. Gut microbiota are exposed to various external and internal factors and form a unique gut-associated immunity maintained through a balancing act among diverse groups of microorganisms. The role of microbiota in dysbiosis of the gut in aiding prostate cancer development has created an urgency for extending research toward comprehension and preventative measures. The gut microbiota varies among persons based on diet, race, genetic background, and geographic location. Bacteriome, mainly, has been linked to GI complications, metabolism, weight gain, and high blood sugar. Studies have shown that manipulating the microbiome (bacteriome, virome, and mycobiome) through the dietary intake of phytochemicals positively influences physical and emotional health, preventing and delaying diseases caused by microbiota. In this review, we discuss the wealth of knowledge about the GI tract and factors associated with dysbiosis-mediated compromised gut immunity. This review also focuses on the relationship of dysbiosis to prostate cancer, the impact of microbial metabolites short-chain fatty acids (SCFAs) on host health, and the phytochemicals improving health while inhibiting prostate cancer.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295966","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}
引用次数: 0
The engineered agonistic anti-CD40 antibody potentiates the antitumor effects of β-glucan by resetting TAMs 经改造的激动型抗 CD40 抗体可通过重置 TAMs 增强β-葡聚糖的抗肿瘤作用。
IF 4.4 4区 医学
Immunology letters Pub Date : 2024-05-27 DOI: 10.1016/j.imlet.2024.106882
Wanpeng Cheng , Ziyi Huang , Yongzhe Hao , Hui Hua , Bo Zhang , Xiangyang Li , Fengqing Fu , Jing Yang , Kuiyang Zheng , Xueguang Zhang , Chunjian Qi
{"title":"The engineered agonistic anti-CD40 antibody potentiates the antitumor effects of β-glucan by resetting TAMs","authors":"Wanpeng Cheng ,&nbsp;Ziyi Huang ,&nbsp;Yongzhe Hao ,&nbsp;Hui Hua ,&nbsp;Bo Zhang ,&nbsp;Xiangyang Li ,&nbsp;Fengqing Fu ,&nbsp;Jing Yang ,&nbsp;Kuiyang Zheng ,&nbsp;Xueguang Zhang ,&nbsp;Chunjian Qi","doi":"10.1016/j.imlet.2024.106882","DOIUrl":"10.1016/j.imlet.2024.106882","url":null,"abstract":"<div><p>Anti-CD40 antibodies (Abs) have been shown to induce antitumor T-cell responses. We reported that the engineered agonistic anti-CD40 Ab (5C11, IgG4 isotype) recognized human CD40 antigen expressed on a human B lymphoblastoid cell line as well as on splenic cells isolated from humanized CD40 mice. Of note, a single high dosage of 5C11 was able to prohibit tumor growth in parallel with an increase in the population of infiltrated CD8<sup>+</sup> T cells. Furthermore, the antitumor effects of 5C11 were enhanced in the presence of β-glucan along with an increase in the population of infiltrated CD8<sup>+</sup> T cells. In addition, the numbers of CD86<sup>+</sup> TAMs and neutrophils were elevated in the combination of 5C11 and β-glucan compared with either 5C11 or β-glucan alone. Furthermore, the abundance of <em>Faecalibaculum</em>, one of the probiotics critical for tumor suppression, was obviously increased in the combination of 5C11 and β-glucan-treated mice. These data reveal a novel mechanism of tumor suppression upon the combination treatment of 5C11 and β-glucan and propose that the combination treatment of agonistic anti-human CD40 antibody 5C11 and β-glucan could be a promising therapeutic strategy for cancer patients.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175586","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}
引用次数: 0
Generation and evaluation of cancer binding capacity of HLA-A2-WT1 complex-targeting antibody 生成和评估 HLA-A2-WT1 复合物靶向抗体的癌症结合能力。
IF 4.4 4区 医学
Immunology letters Pub Date : 2024-05-27 DOI: 10.1016/j.imlet.2024.106881
Xue Yao , Sandro Matosevic
{"title":"Generation and evaluation of cancer binding capacity of HLA-A2-WT1 complex-targeting antibody","authors":"Xue Yao ,&nbsp;Sandro Matosevic","doi":"10.1016/j.imlet.2024.106881","DOIUrl":"10.1016/j.imlet.2024.106881","url":null,"abstract":"<div><p>Wilms’ tumor (WT1), a transcription factor highly expressed in various leukemias and solid tumors, is a highly specific intracellular tumor antigen, requiring presentation through complexation with HLA-restricted peptides.. WT1-derived epitopes are able to assemble with MHC-I and thereby be recognized by T cell receptors (TCR). Identification of new targetable epitopes derived from WT1 on solid tumors is a challenge, but meaningful for the development of therapeutics that could in this way target intracellular oncogenic proteins. In this study, we developed and comprehensively describe methods to validate the formation of the complex of WT1<sub>126–134</sub> and HLA-A2. Subsequently, we developed an antibody fragment able to recognize the extracellular complex on the surface of cancer cells. The single chain variable fragment (scFv) of an established TCR-mimic antibody, specifically recognizing the WT1-derived peptide presented by the HLA-A2 complex, was expressed, purified, and functionally validated using a T2 cell antigen presentation model. Furthermore, we evaluated the potential of the WT1-derived peptide as a targetable extracellular antigen in multiple solid tumor cell lines. Our study describes methodology for the evaluation of WT1-derived peptides as tumor-specific antigen on solid tumors, and may facilitate the selection of potential candidates for future immunotherapy targeting WT1 epitopes.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175584","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}
引用次数: 0
Pathophysiology of cutaneous T-cell lymphomas: Perspective from a French referral centre 皮肤 T 细胞淋巴瘤的病理生理学:来自法国转诊中心的视角。
IF 4.4 4区 医学
Immunology letters Pub Date : 2024-05-25 DOI: 10.1016/j.imlet.2024.106871
Adèle De Masson , Ingrid Lazaridou , Hélène Moins-Teisserenc , Caroline Ram-Wolff , Jérôme Giustiniani , Martine Bagot , Maxime Battistella , Armand Bensussan
{"title":"Pathophysiology of cutaneous T-cell lymphomas: Perspective from a French referral centre","authors":"Adèle De Masson ,&nbsp;Ingrid Lazaridou ,&nbsp;Hélène Moins-Teisserenc ,&nbsp;Caroline Ram-Wolff ,&nbsp;Jérôme Giustiniani ,&nbsp;Martine Bagot ,&nbsp;Maxime Battistella ,&nbsp;Armand Bensussan","doi":"10.1016/j.imlet.2024.106871","DOIUrl":"10.1016/j.imlet.2024.106871","url":null,"abstract":"<div><p>Cutaneous T-cell lymphomas (CTCL) are a diverse group of malignant blood disorders characterized by initial skin infiltration, and sometimes, tumor spreading to lymph nodes, blood, and viscera. Mycosis fungoides is the most common form. Sézary syndrome is a distinctive form of CTCL marked by a significant presence of circulating tumor cells in peripheral blood. These diseases are characterized by the plasticity and heterogeneity of the tumor cells in the different tissue compartments, and a difficulty in identifying these tumor cells for diagnostic purposes and therapeutic monitoring. Progress has been made in the understanding of the pathophysiology of these diseases in recent years, and we provide here a review of these advancements.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158461","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}
引用次数: 0
Corrigendum to “Metformin inhibits the pathogenic functions of AChR-specifc B and Th17 cells by targeting miR-146a” [Immunology Letters 250 (2022) 29–40 on Sep 13, 2022/ Manuscript ID: IMLET-D-22-00159R2, PMID: 36108773] 二甲双胍通过靶向 miR-146a 抑制 AChR-specifc B 细胞和 Th17 细胞的致病功能》的更正 [Immunology Letters 250 (2022) 29-40 on Sep 13, 2022/ Manuscript ID:IMET-D-22-00159R2, PMID: 36108773]
IF 3.3 4区 医学
Immunology letters Pub Date : 2024-05-24 DOI: 10.1016/j.imlet.2024.106866
Yue Hao , Wei Zhao , Lulu Chang , Xingfan Chen , Chonghui Liu , Yang Liu , Lixuan Hou , Yinchun Su , Hao Xu , Yu Guo , Qixu Sun , Lili Mu , Jinghua Wang , Hulun Li , Junwei Han , Qingfei Kong
{"title":"Corrigendum to “Metformin inhibits the pathogenic functions of AChR-specifc B and Th17 cells by targeting miR-146a” [Immunology Letters 250 (2022) 29–40 on Sep 13, 2022/ Manuscript ID: IMLET-D-22-00159R2, PMID: 36108773]","authors":"Yue Hao ,&nbsp;Wei Zhao ,&nbsp;Lulu Chang ,&nbsp;Xingfan Chen ,&nbsp;Chonghui Liu ,&nbsp;Yang Liu ,&nbsp;Lixuan Hou ,&nbsp;Yinchun Su ,&nbsp;Hao Xu ,&nbsp;Yu Guo ,&nbsp;Qixu Sun ,&nbsp;Lili Mu ,&nbsp;Jinghua Wang ,&nbsp;Hulun Li ,&nbsp;Junwei Han ,&nbsp;Qingfei Kong","doi":"10.1016/j.imlet.2024.106866","DOIUrl":"10.1016/j.imlet.2024.106866","url":null,"abstract":"","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000403/pdfft?md5=69fa9f0fc8c588c5a43291863c901948&pid=1-s2.0-S0165247824000403-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141145174","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}
引用次数: 0
N-ethyl-N-nitrosourea (ENU)-induced C-terminal truncation of Runx3 results in autoimmune colitis associated with Th17/Treg imbalance N-乙基-N-亚硝基脲(ENU)诱导的Runx3 C端截短会导致与Th17/Treg失衡相关的自身免疫性结肠炎。
IF 4.4 4区 医学
Immunology letters Pub Date : 2024-05-22 DOI: 10.1016/j.imlet.2024.106869
Yi-Ting Chen , Yi-Mei Chang , Yu-Ling Chen , Yu-Hsuan Su , Chia-Chi Liao , Tien-Huang Chiang , Wen-Yu Chen , Yu-Chia Su
{"title":"N-ethyl-N-nitrosourea (ENU)-induced C-terminal truncation of Runx3 results in autoimmune colitis associated with Th17/Treg imbalance","authors":"Yi-Ting Chen ,&nbsp;Yi-Mei Chang ,&nbsp;Yu-Ling Chen ,&nbsp;Yu-Hsuan Su ,&nbsp;Chia-Chi Liao ,&nbsp;Tien-Huang Chiang ,&nbsp;Wen-Yu Chen ,&nbsp;Yu-Chia Su","doi":"10.1016/j.imlet.2024.106869","DOIUrl":"10.1016/j.imlet.2024.106869","url":null,"abstract":"<div><p>Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory intestinal disease that affects people around the world. The primary cause of IBD is an imbalance in the host immune response to intestinal flora. Several human genes, including <em>IL10, STAT3, IRGM, ATG16L1, NOD2</em> and <em>RUNX3</em>, are associated with inappropriate immune responses in IBD. It has been reported that homozygous Runx3-knockout (ko) mice spontaneously develop colitis. However, the high mortality rate in these mice within the first two weeks makes it challenging to study the role of Runx3 in colitis. To address this issue, a spontaneous colitis (<em>SC</em>) mouse model carrying a C-terminal truncated form of Runx3 with Tyr319stop point mutation has been generated. After weaning, <em>SC</em> mice developed spontaneous diarrhea and exhibited prominent enlargement of the colon, accompanied by severe inflammatory cell infiltration. Results of immunofluorescence staining showed massive CD4<sup>+</sup> T cell infiltration in the inflammatory colon of <em>SC</em> mice. Colonic IL-17A mRNA expression and serum IL-17A level were increased in <em>SC</em> mice. CD4<sup>+</sup> T cells from <em>SC</em> mice produced stronger IL-17A than those from wildtype mice in Th17-skewing conditions <em>in vitro</em>. In addition, the percentages of Foxp3<sup>+</sup> Treg cells as well as the RORγt<sup>+</sup>Foxp3<sup>+</sup> Treg subset, known for its role in suppressing Th17 response in the gut, were notably lower in colon lamina propria of <em>SC</em> mice than those in WT mice. Furthermore, transfer of total CD4<sup>+</sup> T cells from <em>SC</em> mice, but not from wildtype mice, into Rag1-ko host mice resulted in severe autoimmune colitis. In conclusion, the C-terminal truncated Runx3 caused autoimmune colitis associated with Th17/Treg imbalance. The <em>SC</em> mouse model is a feasible approach to investigate the effect of immune response on spontaneous colitis.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000439/pdfft?md5=76ecaebb9aa84b84351dd330a077eb80&pid=1-s2.0-S0165247824000439-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093021","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}
引用次数: 0
The Th1/Th2 paradigm: A misrepresentation of helper T cell plasticity Th1/Th2范式:辅助性 T 细胞可塑性的错误表述
IF 4.4 4区 医学
Immunology letters Pub Date : 2024-05-22 DOI: 10.1016/j.imlet.2024.106870
Noah P. Rogozynski, Brian Dixon
{"title":"The Th1/Th2 paradigm: A misrepresentation of helper T cell plasticity","authors":"Noah P. Rogozynski,&nbsp;Brian Dixon","doi":"10.1016/j.imlet.2024.106870","DOIUrl":"https://doi.org/10.1016/j.imlet.2024.106870","url":null,"abstract":"<div><p>For decades, the Th1/2 paradigm has been used to classify immune responses as either Th1 or Th2-biased. However, in recent years, a staggering amount of evidence has emerged to support rejection of the classical Th1/Th2 paradigm, such as the discoveries of new helper T cell subsets, helper T cell plasticity and protective mixed-Th1/Th2 responses. This opinion piece investigates the shortcomings of classical Th1/Th2 paradigm in the context of recent works, with the goal of facilitating the development of newer models to represent the diversity of Th cells.</p></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0165247824000440/pdfft?md5=1c6502250377627b8edf98575777977c&pid=1-s2.0-S0165247824000440-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089994","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}
引用次数: 0
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