Saumendra N Sarkar, Munesh K Harioudh, Lulu Shao, Joseph Perez, Arundhati Ghosh
{"title":"The Many Faces of Oligoadenylate Synthetases.","authors":"Saumendra N Sarkar, Munesh K Harioudh, Lulu Shao, Joseph Perez, Arundhati Ghosh","doi":"10.1089/jir.2023.0098","DOIUrl":"10.1089/jir.2023.0098","url":null,"abstract":"<p><p>2'-5' Oligoadenylate synthetases (OAS) are interferon-stimulated genes that are most well-known to protect hosts from viral infections. They are evolutionarily related to an ancient family of Nucleotidyltransferases, which are primarily involved in pathogen-sensing and innate immune response. Classical function of OAS proteins involves double-stranded RNA-stimulated polymerization of adenosine triphosphate in 2'-5' oligoadenylates (2-5A), which can activate the latent RNase (RNase L) to degrade RNA. However, accumulated evidence over the years have suggested alternative mode of antiviral function of several OAS family proteins. Furthermore, recent studies have connected some OAS proteins with wider function beyond viral infection. Here, we review some of the canonical and noncanonical functions of OAS proteins and their mechanisms.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"487-494"},"PeriodicalIF":1.9,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10654648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41122431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Annihilation of Non-small Cell Lung Cancer by NKG2D CAR-T Cells Produced from T Cells from Peripheral Blood of Healthy Donors.","authors":"Jinhong Jiang, Yonghua Liu, Yuxiao Zeng, Bingmu Fang, Yongping Chen","doi":"10.1089/jir.2023.0043","DOIUrl":"10.1089/jir.2023.0043","url":null,"abstract":"<p><p>Some progress has been made in immunotherapy with chimeric antigen receptor (CAR)-T cells targeting NKG2D-NKG2DL with the purpose of eradicating solid tumors. Non-small cell lung cancer (NSCLC) has been shown to express NKG2DL. This study hence evaluated the therapeutic effect of NKG2D CAR-T cells on NSCLC. Accordingly, NKG2D CAR-T cells were obtained from diverse human autologous T cell sources. T cells from peripheral blood T lymphocytes of healthy volunteers (without NKG2D CAR insertion) were used as NT-T cells. Coculture of effector cells (CAR-T cells or NT-T cells) with target cells (NSCLC cells such as PC-9 or NCL-H460 cells) was performed at different ratios. The cytotoxicity of CAR-T cells was examined using lactate dehydrogenase assay kits. Murine xenograft assay was conducted to investigate the <i>in vivo</i> antitumor effect of CAR-T cells. Cytokines secreted from CAR-T cells were assessed by enzyme-linked immunosorbent assay. CAR-T cell infiltration into xenografts was observed through immunochemical assay. Based on the results, NKG2DL was highly expressed in NSCLC cells. Compared with NT-T cells, NKG2D CAR-T cells from different sources of T cells delivered stronger toxicity, and secreted more effector and memory function-related cytokines to NSCLC cells, and those from the peripheral blood of healthy donors (H-T cells) exhibited the strongest effect. Furthermore, compared with NT-T cells, H-T cells and NKG2D CAR-T cells from NSCLC patients' peripheral blood diminished tumor, improved survival, increased body weight and tumor-infiltrating capacity, and upregulated serum IFN-γ level in NOG mice. Collectively speaking, NKG2D CAR-T cells exhibit a robust effect on eradicating NSCLC in a NKG2DL-dependent manner, thus making themselves a promising therapeutic candidate for NSCLC patients.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 10","pages":"445-454"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Conversation with Judy Lieberman.","authors":"","doi":"10.1089/jir.2023.29055.int","DOIUrl":"10.1089/jir.2023.29055.int","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 10","pages":"441-444"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role and Potential Regulatory Mechanism of <i>STING</i> Modulated Macrophage Apoptosis and Differentiation in Severe Acute Pancreatitis-Associated Lung Injury.","authors":"Yiqiu Peng, Yingying Li, Yuxi Yang, Tingjuan Shi, Ruixia Liu, Yingyi Luan, Chenghong Yin","doi":"10.1089/jir.2023.0077","DOIUrl":"10.1089/jir.2023.0077","url":null,"abstract":"<p><p>This study aims to investigate the role of STING in promoting macrophage apoptosis and regulating macrophage polarization in severe acute pancreatitis (SAP)-associated lung injury <i>in vitro</i> and <i>in vivo</i>. A murine model was established by intraperitoneal injection of caerulein and lipopolysaccharide (LPS). Meanwhile, ANA-1 cells were stimulated with LPS to induce apoptosis <i>in vitro</i>. More primary alveolar macrophages underwent apoptosis and M1 macrophage polarization in the SAP group compared with the control group, which was reversed by inhibiting STING. When ANA-1 cells were induced into M2-type macrophages, the reduction of M1 macrophage markers was accompanied by a decrease of LPS-induced apoptosis. Finally, the inhibitory effect of C-176 on STING ameliorates lung injury and inflammation by adjusting macrophage polarization and rescuing apoptosis. Therefore, inhibiting STING could be a new therapeutic strategy for treating acute pancreatitis-associated lung injury.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 10","pages":"455-468"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Call for Special Issue Papers:</i> The \"Yin-Yang\" Activities of Tumor-Induced Inflammatory Cytokines for Cancer Immunotherapy, Detection and Prognosis.","authors":"Yan Ma, Sanjay Mukherjee, Jing Ma","doi":"10.1089/jir.2023.29056.cfp","DOIUrl":"10.1089/jir.2023.29056.cfp","url":null,"abstract":"","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":"43 10","pages":"439-440"},"PeriodicalIF":2.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10775213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41203393","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}
Jeremy Ardanuy, Karen M Scanlon, Ciaran Skerry, Nicholas H Carbonetti
{"title":"DNA-Dependent Interferon Induction and Lung Inflammation in <i>Bordetella pertussis</i> Infection.","authors":"Jeremy Ardanuy, Karen M Scanlon, Ciaran Skerry, Nicholas H Carbonetti","doi":"10.1089/jir.2023.0066","DOIUrl":"10.1089/jir.2023.0066","url":null,"abstract":"<p><p>Pertussis, caused by <i>Bordetella pertussis</i>, is a resurgent respiratory disease but the molecular mechanisms underlying pathogenesis are poorly understood. We recently showed the importance of type I and type III interferon (IFN) induction and signaling for the development of lung inflammation in <i>B. pertussis</i>-infected mouse models. Classically, these IFNs are induced by signaling through a variety of pattern recognition receptors (PRRs) on host cells. Here, we found that the PRR signaling adaptor molecules MyD88 and TRIF contribute to IFN induction and lung inflammatory pathology during <i>B. pertussis</i> infection. However, the PRRs Toll-like receptors (TLR) 3 and TLR4, which signal through TRIF and MyD88, respectively, played no role in IFN induction. Instead, the DNA-sensing PRRs, TLR9 and STING, were important for induction of type I/III IFN and promotion of inflammatory pathology, indicating that DNA is a major inducer of lung IFN responses in <i>B. pertussis</i> infection. These results increase our understanding of this host-pathogen interaction and identify potential targets for host-directed therapies to reduce <i>B. pertussis</i>-mediated pathology.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":" ","pages":"478-486"},"PeriodicalIF":1.9,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10599430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10483283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Characterization of IL-10 Family of Cytokines in Acute and Convalescent COVID-19 Individuals.","authors":"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","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}
{"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}
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}
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}