Journal of Interferon and Cytokine Research最新文献

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Characterization of IL-10 Family of Cytokines in Acute and Convalescent COVID-19 Individuals. 急性和康复新冠肺炎患者IL-10细胞因子家族的特征。
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-10-01 Epub Date: 2023-09-14 DOI: 10.1089/jir.2023.0075
Anuradha Rajamanickam, Pavan Kumar Nathella, Nandhini Selvaraj, Murhekar Manoj, Jeromie Wesley Vivian Thangaraj, Santhosh Kumar Muthusamy, Girish Kumar Chethrapilly Purushothaman, Tarun Bhatnagar, Manickam Ponnaiah, Sabarinathan Ramasamy, Saravanakumar Velusamy, Subash Babu
{"title":"Characterization of IL-10 Family of Cytokines in Acute and Convalescent COVID-19 Individuals.","authors":"Anuradha Rajamanickam,&nbsp;Pavan Kumar Nathella,&nbsp;Nandhini Selvaraj,&nbsp;Murhekar Manoj,&nbsp;Jeromie Wesley Vivian Thangaraj,&nbsp;Santhosh Kumar Muthusamy,&nbsp;Girish Kumar Chethrapilly Purushothaman,&nbsp;Tarun Bhatnagar,&nbsp;Manickam Ponnaiah,&nbsp;Sabarinathan Ramasamy,&nbsp;Saravanakumar Velusamy,&nbsp;Subash Babu","doi":"10.1089/jir.2023.0075","DOIUrl":"10.1089/jir.2023.0075","url":null,"abstract":"<p><p>Cytokines are major players in orchestrating inflammation, disease pathogenesis, and severity during COVID-19. Members of the interleukin (IL)-10 family of cytokines play important roles in regulating immune responses to various inflammatory and infectious diseases. However, the role of the IL-10 family of cytokines in COVID-19 remains elusive. Hence, we determined the plasma levels of the IL-10 family of cytokines (IL-10, IL-19, IL-20, IL-22, and IL-24) in 7 groups of COVID-19 individuals, based on days since real-time reverse transcriptase-polymerase chain reaction confirmation of SARS-CoV-2 infection. Our data show that the levels of IL-10, IL-19, IL-20, IL-22, and IL-24 cytokines decreased from days 15-30 to days 61-90 and plateaued thereafter. Severe COVID-19 patients exhibit increased plasma levels of IL-10, IL-19, IL-20, IL-22, and IL-24 compared to mild patients. Thus, our study provides evidence of alterations in the plasma levels of the IL-10 family of cytokines in convalescent COVID-19 individuals.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"469-477"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10245043","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
A Novel Inactive Isoform with a Restored Reading Frame Is Expressed from the Human Interferon Lambda 4 TT Allele at rs368234815. 从人干扰素Lambda 4 TT等位基因rs368234815表达一种新的具有恢复阅读框的非活性异构体。
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 Epub Date: 2023-03-07 DOI: 10.1089/jir.2022.0199
Seema Bharatiya, Aditya Agarwal, Sreedhar Chinnaswamy
{"title":"A Novel Inactive Isoform with a Restored Reading Frame Is Expressed from the Human Interferon Lambda 4 TT Allele at rs368234815.","authors":"Seema Bharatiya, Aditya Agarwal, Sreedhar Chinnaswamy","doi":"10.1089/jir.2022.0199","DOIUrl":"10.1089/jir.2022.0199","url":null,"abstract":"<p><p>The TT allele of the dinucleotide variant rs368234815 (TT/ΔG) abolishes the open reading frame (ORF) created by the ancestral ΔG allele of the human interferon lambda 4 (<i>IFNL4</i>) gene, thus preventing the expression of a functional IFN-λ4 protein. While probing the expression of IFN-λ4 in human peripheral blood mononuclear cells (PBMCs), using a monoclonal antibody that binds to the C-terminus of IFN-λ4, surprisingly, we observed that PBMCs obtained from TT/TT genotype individuals could also express proteins that reacted with the IFN-λ4-specific antibody. We confirmed that these products did not emanate from the <i>IFNL4</i> paralog, IF1IC2 gene. Using cell lines and overexpressing human <i>IFNL4</i> gene constructs, we obtained evidence from Western blots to show that the TT allele could express a protein that reacted with the IFN-λ4 C-terminal-specific antibody. It had a molecular weight similar if not identical to IFN-λ4 expressed from the ΔG allele. Furthermore, the same start and stop codons used by the ΔG allele were used to express the novel isoform from the TT allele suggesting that a restoration of the ORF had occurred in the body of the mRNA. However, this TT allele isoform did not induce any IFN-stimulated gene expression. Our data do not support a ribosomal frameshift that leads to the expression of this new isoform, implying that an alternate splicing event may be responsible. An N-terminal-specific monoclonal antibody did not react with the novel protein isoform suggesting that the alternate splicing event likely occurs beyond exon 2. The new isoform is glycosylated similar to the functional IFN-λ4 and is also secreted. Furthermore, we show that the ΔG allele can also potentially express a similarly frameshifted isoform. The splicing event that leads to the generation of these novel isoforms and their functional significance remains to be elucidated.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"370-378"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10299098","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
Deletion of Interferon Lambda Receptor Elucidates Susceptibility to the Murine Model of Biliary Atresia. 干扰素Lambda受体的缺失阐明了对小鼠胆道闭锁模型的易感性。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 DOI: 10.1089/jir.2023.0046
Stephen J Hartman, Madeleine A Weiss, Haley M Temple, Bryan Donnelly, Rajamouli Pasula, Holly M Poling, Monica McNeal, Sujit K Mohanty, Greg M Tiao
{"title":"Deletion of Interferon Lambda Receptor Elucidates Susceptibility to the Murine Model of Biliary Atresia.","authors":"Stephen J Hartman, Madeleine A Weiss, Haley M Temple, Bryan Donnelly, Rajamouli Pasula, Holly M Poling, Monica McNeal, Sujit K Mohanty, Greg M Tiao","doi":"10.1089/jir.2023.0046","DOIUrl":"10.1089/jir.2023.0046","url":null,"abstract":"<p><p>Biliary atresia (BA) is a life-threatening cholangiopathy occurring in infancy, the most common indication for pediatric liver transplantation. The etiology of BA remains unknown; however, a viral etiology has been proposed as multiple viruses have been detected in explants of infants afflicted with BA. In the murine model of BA, Rhesus rotavirus (RRV) infection of newborn BALB/c pups results in a cholangiopathy that mirrors human BA. Infected BALB/c pups experience 100% symptomatology and mortality, while C57BL/6 mice are asymptomatic. Interferon-λ (IFN-λ) is an epithelial cytokine that provides protection against viral infection. We demonstrated that IFN-λ is highly expressed in C57BL/6, leading to reduced RRV replication. RRV-infection of C57BL/6 IFN-λ receptor knockout (C57BL/6 IFN-λR KO) pups resulted in 90% developing obstructive symptoms and 45% mortality with a higher viral titer in bile ducts and profound periportal inflammation compared to C57BL/6. Histology revealed complete biliary obstruction in symptomatic C57BL/6 IFN-λR KO pups, while C57BL/6 ducts were patent. These findings suggest that IFN-λ is critical in preventing RRV replication. Deficiency in IFN-λ permits RRV infection, which triggers the inflammatory cascade causing biliary obstruction. Further IFN-λ study is warranted as it may play an important role in infant susceptibility to BA.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"427-434"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41135722","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
IFNL4 Genotype Frequencies in Asian Populations Support Shorter Duration Therapy with Sofosbuvir-Based Hepatitis C Virus Regimens to Increase the Number Cured. 亚洲人群中IFNL4基因型频率支持使用基于索非布韦的丙型肝炎病毒方案进行短期治疗,以增加治愈人数。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 Epub Date: 2023-06-22 DOI: 10.1089/jir.2023.0022
Thomas R O'Brien, Mei-Hsuan Lee, Eleanor Wilson, Shyam Kottilil
{"title":"<i>IFNL4</i> Genotype Frequencies in Asian Populations Support Shorter Duration Therapy with Sofosbuvir-Based Hepatitis C Virus Regimens to Increase the Number Cured.","authors":"Thomas R O'Brien, Mei-Hsuan Lee, Eleanor Wilson, Shyam Kottilil","doi":"10.1089/jir.2023.0022","DOIUrl":"10.1089/jir.2023.0022","url":null,"abstract":"<p><p>Globally, ∼56.8 million people are chronically infected with hepatitis C virus (HCV), with about half residing in Asia. The cost and efficiency of delivering regimens based on direct-acting antiviral agents for HCV are important considerations in implementing these curative treatments. For sofosbuvir-based regimens, most patients are treated for 12 weeks; however, treatment for 8 weeks has been shown to cure HCV infection in 95% of patients without cirrhosis. Furthermore, virological failure after 8-week treatment occurs in only 1%-2% of individuals without cirrhosis, who have a favorable <i>IFNL4</i> genotype, which is present in >50% of South Asians and >80% of East Asians. We propose that sofosbuvir-based treatment for 8 weeks, or perhaps shorter, would yield high response rate regimens in Asian countries and markedly increase the number of patients who could be cured for a given cost of the medication. We propose that a noninferiority trial in an East Asian population be conducted to test this hypothesis.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"435-438"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10299423","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
Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia. 中和III型干扰素的自身抗体在2019年严重冠状病毒肺炎患者中不常见。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 Epub Date: 2023-05-29 DOI: 10.1089/jir.2023.0003
Martti Vanker, Karita Särekannu, Arnaud Fekkar, Sofie Eg Jørgensen, Liis Haljasmägi, Anne Kallaste, Kalle Kisand, Margus Lember, Pärt Peterson, Madhvi Menon, Tracy Hussell, Sean Knight, James Moore-Stanley, Paul Bastard, Shen-Ying Zhang, Trine H Mogensen, Quentin Philippot, Qian Zhang, Anne Puel, Jean-Laurent Casanova, Kai Kisand
{"title":"Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia.","authors":"Martti Vanker, Karita Särekannu, Arnaud Fekkar, Sofie Eg Jørgensen, Liis Haljasmägi, Anne Kallaste, Kalle Kisand, Margus Lember, Pärt Peterson, Madhvi Menon, Tracy Hussell, Sean Knight, James Moore-Stanley, Paul Bastard, Shen-Ying Zhang, Trine H Mogensen, Quentin Philippot, Qian Zhang, Anne Puel, Jean-Laurent Casanova, Kai Kisand","doi":"10.1089/jir.2023.0003","DOIUrl":"10.1089/jir.2023.0003","url":null,"abstract":"<p><p>Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; <i>P</i> < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"379-393"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301604","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
IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa. 东非儿童伯基特淋巴瘤的IFNL4基因型和风险。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 Epub Date: 2023-06-27 DOI: 10.1089/jir.2023.0014
Francine S Baker, Jeanny Wang, Oscar Florez-Vargas, Nathan R Brand, Martin D Ogwang, Patrick Kerchan, Steven J Reynolds, Constance N Tenge, Pamela A Were, Robert T Kuremu, Walter N Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Isaac Otim, Ismail D Legason, Hadijah Nabalende, George Chagaluka, Nora Mutalima, Eric Borgstein, George N Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, Elizabeth M Molyneux, Robert Newton, Ludmila Prokunina-Olsson, Sam M Mbulaiteye
{"title":"<i>IFNL4</i> Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa.","authors":"Francine S Baker, Jeanny Wang, Oscar Florez-Vargas, Nathan R Brand, Martin D Ogwang, Patrick Kerchan, Steven J Reynolds, Constance N Tenge, Pamela A Were, Robert T Kuremu, Walter N Wekesa, Nestory Masalu, Esther Kawira, Tobias Kinyera, Isaac Otim, Ismail D Legason, Hadijah Nabalende, George Chagaluka, Nora Mutalima, Eric Borgstein, George N Liomba, Steve Kamiza, Nyengo Mkandawire, Collins Mitambo, Elizabeth M Molyneux, Robert Newton, Ludmila Prokunina-Olsson, Sam M Mbulaiteye","doi":"10.1089/jir.2023.0014","DOIUrl":"10.1089/jir.2023.0014","url":null,"abstract":"<p><p>Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the <i>IFNL4</i> gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (<i>IFNL4</i>-dG) is most common (up to 78%) in West sub-Saharan Africa (SSA), compared to 35% of Europeans and 5% of individuals from East Asia. The negative selection of <i>IFNL4</i>-dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between <i>IFNL4</i> genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case-control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, <i>P. falciparum</i> infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within <i>IFNL4</i> (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6-9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of <i>IFNL4</i>-dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"394-402"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10623078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10298542","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
Characterization of Monoclonal Antibodies to Measure Cell Surface Protein Levels of Human Interferon-Lambda Receptor 1. 用于测量人干扰素λ受体1的细胞表面蛋白水平的单克隆抗体的特性。
IF 2.3 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 Epub Date: 2023-07-27 DOI: 10.1089/jir.2023.0040
Nicole A de Weerd, Olamide Ogungbola, Xinyun Liu, Antony Y Matthews, Amina Ismail, Julian P Vivian, San S Lim, D Lorne Tyrrell, Niru Putcha, Mike Skawinski, Harold Dickensheets, Thomas B Lavoie, Raymond P Donnelly, Paul J Hertzog, Deanna M Santer
{"title":"Characterization of Monoclonal Antibodies to Measure Cell Surface Protein Levels of Human Interferon-Lambda Receptor 1.","authors":"Nicole A de Weerd,&nbsp;Olamide Ogungbola,&nbsp;Xinyun Liu,&nbsp;Antony Y Matthews,&nbsp;Amina Ismail,&nbsp;Julian P Vivian,&nbsp;San S Lim,&nbsp;D Lorne Tyrrell,&nbsp;Niru Putcha,&nbsp;Mike Skawinski,&nbsp;Harold Dickensheets,&nbsp;Thomas B Lavoie,&nbsp;Raymond P Donnelly,&nbsp;Paul J Hertzog,&nbsp;Deanna M Santer","doi":"10.1089/jir.2023.0040","DOIUrl":"10.1089/jir.2023.0040","url":null,"abstract":"<p><p>Type III interferons (IFN-lambdas, IFN-λs) are important antiviral cytokines that can also modulate immune responses by acting through a heterodimeric receptor composed of the specific and limited expressed IFN-λR1 chain and the ubiquitous IL-10R2 chain, which is shared with IL-10 family cytokines. Conflicting data have been reported regarding which cells express the IFN-λR1 subunit and directly respond to IFN-λs. This is, in part, owing to transcript levels of the IFN-λR1 gene, <i>IFNLR1</i>, not always correlating with cell surface protein levels. In this study, we tested a panel of novel monoclonal antibodies (mAbs) that specifically recognize human IFN-λR1. Initially, antigen specificity was confirmed by enzyme-linked immunosorbent assay (ELISA), from which a subset of antibodies was selected for additional flow cytometry and neutralization assays. We further characterized two antibodies based on their strong ELISA binding activity (HLR1 and HLR14) and found only HLR14 could reliably detect cell surface IFN-λR1 protein on a variety of cell lines by flow cytometry. HLR14 could also detect IFN-λR1 protein on certain primary human blood cells, including plasmacytoid dendritic cells and B cells from peripheral blood. Availability of the HLR14 mAb will enable the quantification of IFN-λR1 protein levels on cells and better characterization of the cell specificity of the IFN-λ response.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"403-413"},"PeriodicalIF":2.3,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301939","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: 2
Roles and Effects of Interferon Lambda Signaling in the Context of Bacterial Infections. 干扰素Lambda信号传导在细菌感染中的作用和影响。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 Epub Date: 2023-06-08 DOI: 10.1089/jir.2023.0037
Da'Kuawn Johnson, Nicholas Carbonetti
{"title":"Roles and Effects of Interferon Lambda Signaling in the Context of Bacterial Infections.","authors":"Da'Kuawn Johnson, Nicholas Carbonetti","doi":"10.1089/jir.2023.0037","DOIUrl":"10.1089/jir.2023.0037","url":null,"abstract":"<p><p>Type III interferon, or interferon lambda (IFNλ), was discovered 20 years ago and has been studied primarily for its role in combatting viral infections. However, it is also induced in response to certain bacterial infections but its roles and effects in this context are relatively poorly understood. In this mini review, we discuss the roles of IFNλ signaling in bacterial infections, highlighting its deleterious or protective effects for different infections. We also discuss a couple of recent studies showing that some bacteria possess defense mechanisms against the effects of IFNλ. We hope that this review will spur further investigation into the roles of IFNλ in the context of bacterial infections and will promote considerations of its therapeutic potential for these infections.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"363-369"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10301649","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
Synthetic Heterodimers of Type III Interferon Receptors Require TYK2 for STAT Activation. III型干扰素受体的合成杂二聚体需要TYK2来激活STAT。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 DOI: 10.1089/jir.2023.0039
Emily V Mesev, Emma G Guare, Alexander Ploss, Jared E Toettcher
{"title":"Synthetic Heterodimers of Type III Interferon Receptors Require TYK2 for STAT Activation.","authors":"Emily V Mesev, Emma G Guare, Alexander Ploss, Jared E Toettcher","doi":"10.1089/jir.2023.0039","DOIUrl":"10.1089/jir.2023.0039","url":null,"abstract":"<p><p>Type III interferons (IFN-λ) are central to host defense against viral infection of epithelial barrier surfaces. IFN-λ binding to its receptor induces a JAK-STAT cascade through kinases Janus-associated kinase 1 (JAK1) and tyrosine kinase 2 (TYK2), which are associated on either subunit of the heterodimeric type III IFN receptor. Recent studies have shown that TYK2 is not necessary for IFN-λ to signal, in contrast to IFN-α, which uses the same JAK-STAT pathway activated by the type I IFN receptor. The mechanism for this differential TYK2 requirement is unknown. Our study uses synthetic IFN receptors in TYK2-deficient U2OS epithelial cells to define the processes in type I and III IFN signaling that require TYK2. We find that TYK2 deficiency reduces signaling equally from heterodimers of either type I or III IFN receptor intracellular domains. In contrast, JAK1-associated homodimers of IFNAR2 or IFNLR1 are both fully signaling competent even in the absence of TYK2. These results suggest that heterodimerization of the type III IFN receptor is insufficient to confer TYK2-independent signaling. Thus, we propose that noncanonical receptor complexes may participate in endogenous type III IFN signaling to confer TYK2-independent signaling downstream of IFN-λ stimulation.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 9","pages":"414-426"},"PeriodicalIF":1.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10517332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125227","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 Interferon-Lambda Family Celebrates 20 Years of Scientific Discovery. 干扰素Lambda家族庆祝科学发现20周年。
IF 1.9 4区 医学
Journal of Interferon and Cytokine Research Pub Date : 2023-09-01 DOI: 10.1089/jir.2023.0122
Raymond P Donnelly, Ludmila Prokunina-Olsson
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