Immunological Investigations最新文献

{"title":"CAR-T Therapy Targets Extra Domain B of Fibronectin Positive Solid Tumor Cells.","authors":"Jie Tang, Nan Liu, Yongjie Zhu, Yi Li, Xudong Zhao","doi":"10.1080/08820139.2023.2264332","DOIUrl":"10.1080/08820139.2023.2264332","url":null,"abstract":"<p><strong>Background: </strong>CAR-T cell immunotherapy has achieved remarkable success in malignant B-cell malignancies, but progress in solid tumors is slow, and one of the key reasons is the lack of ideal targets. Cancer-specific extra domain B of fibronectin (EDB-FN) is widely upregulated in solid tumors and expressed at low levels in normal tissues. Many imaging and targeted cancer therapies based on EDB-FN targets have been developed and tested in clinical trials, making EDB-FN an ideal target for immunotherapy.</p><p><strong>Methods: </strong>We constructed two EDB-FN-targeted CAR-Ts based on the peptide APT0 and the single-chain antibody CGS2 in a lentiviral infection manner for the first time. Luciferase cytotoxicity assay to assess CAR-T killing of tumor cells. An enzyme-linked immunosorbent assay was used to detect the release of the cytokine IFN-γ. Fluorescence imaging to evaluate the dynamics of CAR-T cell and tumor cell coculture. Knockdown assays were used to validate the target specificity of CAR-T cells.</p><p><strong>Results: </strong>In this research, two CAR-Ts targeting EDB-FN, APT0 CAR-T, and CGS2 CAR-T, were constructed. In vitro, both CAR-T cells produced broad-spectrum killing of multiple EDB-FN-positive solid tumor cell lines and were accompanied by cytokine IFN-γ release. Regarding safety, the two CAR-T cells did not affect T cells' normal growth and proliferation and were not toxic to HEK-293T human embryonic kidney epithelial cells.</p><p><strong>Conclusion: </strong>APT0 CAR-T and CGS2 CAR-T cells are two new CAR-Ts targeting EDB-FN. Both CAR-T cells can successfully identify and specifically kill various EDB-FN-positive solid tumor cells with potential clinical applications.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"985-996"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41182487","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":"Immunological Assessment of Recent Immunotherapy for Colorectal Cancer.","authors":"Subhadeep Das, Diptikanta Acharya","doi":"10.1080/08820139.2023.2264906","DOIUrl":"10.1080/08820139.2023.2264906","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the third most prevalent malignancy with increased incidence and mortality rates worldwide. Traditional treatment approaches have attempted to efficiently target CRC; however, they have failed in most cases, owing to the cytotoxicity and non-specificity of these therapies. Therefore, it is essential to develop an effective alternative therapy to improve the clinical outcomes in heterogeneous CRC cases. Immunotherapy has transformed cancer treatment with remarkable efficacy and overcomes the limitations of traditional treatments. With an understanding of the cancer-immunity cycle and tumor microenvironment evolution, current immunotherapy approaches have elicited enhanced antitumor immune responses. In this comprehensive review, we outline the latest advances in immunotherapy targeting CRC and provide insights into antitumor immune responses reported in landmark clinical studies. We focused on highlighting the combination approaches that synergistically induce immune responses and eliminate immunosuppression. This review aimed to understand the limitations and potential of recent immunotherapy clinical studies conducted in the last five years (2019-2023) and to transform this knowledge into a rational design of clinical trials intended for effective antitumor immune responses in CRC.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1065-1095"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41118974","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 Crosstalk Between Castration-Resistant Prostate Cancer Cells, M2 Macrophages, and NK Cells: Role of the ATM-PI3K/AKT-PD-L1 Pathway.","authors":"Hongliang Jin, Jin Zhu, Rui Xuan, Yibin Zhou, Boxin Xue, Dongrong Yang, Jie Gao, Yachen Zang, Lijun Xu","doi":"10.1080/08820139.2023.2258930","DOIUrl":"10.1080/08820139.2023.2258930","url":null,"abstract":"<p><p>Castration-resistant prostate cancer (CRPC) in males is associated with a poor prognosis and a higher risk of treatment-related adverse effects, with high mortality among cancers globally. It is thus imperative to explore novel potential molecules with dual therapeutic and biomarker functions. Based on the recent research findings, the expression levels of ataxia telangiectasia mutant kinase (ATM) in prostate cancer (PC) tissues collected from CRPC patients were higher than hormone-dependent PC patients. Using CRPC cell lines (C4-2 and CWR22Rv1), the transwell chamber experiments revealed ATM promoted macrophage recruitment in CRPC cells <i>in vitro</i> via C-X-C motif chemokine ligand 12 (CXCL12). Further i<i>n vitro</i> investigations demonstrated that polarized macrophages prevented NK cell recruitment and reduced the immunocidal activity of NK cells against CRPC cell lines. Moreover, ATM boosted programmed death receptor ligand 1 (PD-L1) expression while inhibiting NK group 2D (NKG2D) ligand expression in selected cell lines via PI3K/AKT signaling pathway. The <i>in vivo</i> investigations revealed ATM induced proliferation of CRPC and macrophage recruitment, while the NK cell recruitment was found to suppress ATM expression and CRPC proliferation. In conclusion, it could be demonstrated that inhibiting ATM increased the susceptibility of CRPC to NK cell inhibitors by dampening the CXCL12 and PI3K/AKT-PD-L1 pathways, thereby offering a novel and individualized treatment protocol for treating CRPC.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"941-965"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41119347","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":"Dengue Vaccination: Towards a New Dawn of Curbing Dengue Infection.","authors":"Sidhant Jain, Neha Vimal, Nilza Angmo, Madhumita Sengupta, Suraj Thangaraj","doi":"10.1080/08820139.2023.2280698","DOIUrl":"10.1080/08820139.2023.2280698","url":null,"abstract":"<p><p>Dengue is an infectious disease caused by dengue virus (DENV) and is a serious global burden. Antibody-dependent enhancement and the ability of DENV to infect immune cells, along with other factors, lead to fatal Dengue Haemorrhagic Fever and Dengue Shock Syndrome. This necessitates the development of a robust and efficient vaccine but vaccine development faces a number of hurdles. In this review, we look at the epidemiology, genome structure and cellular targets of DENV and elaborate upon the immune responses generated by human immune system against DENV infection. The review further sheds light on various challenges in development of a potent vaccine against DENV which is followed by presenting a current account of different vaccines which are being developed or have been licensed.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1096-1149"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153760","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":"Rat Experimental Autoimmune Gastritis Model.","authors":"Liubov Beduleva, Kseniya Fomina, Alexandr Sidorov, Alexey Terentiev, Pavel Ivanov, Igor Menshikov","doi":"10.1080/08820139.2023.2283103","DOIUrl":"10.1080/08820139.2023.2283103","url":null,"abstract":"<p><strong>Background: </strong>Autoimmune gastritis (AIG) is an autoimmune disease of the stomach characterized by the destruction of the oxyntic mucosa, which stops producing acid and becomes both functionally and morphologically atrophic. The pathogenic mechanisms behind the disease are still poorly understood. There is no early diagnosis and specific AIG therapy. To elucidate the pathogenesis of AIG, to search for early diagnostic markers, as well as to test new therapeutic approaches, an adequate and easily reproducible experimental model for autoimmune gastritis (EAG) is needed. Existing EAG models have some limitations, including slow development of signs, absence of advanced gastritis, irrational use of animals to obtain antigen. The aim was to find out whether it is possible to cause autoimmune gastritis similar to human disease in Wistar rats through immunization with a homologous gastric mucosa extract.</p><p><strong>Methods: </strong>Wistar rats were immunized with gastric mucosa extract. Histology studies and evaluation of serological parameters were performed 56 and 91 days later.</p><p><strong>Results: </strong>Destruction of oxyntic glands by infiltrating T lymphocytes were detected in rats on 56 and 91 days after initial immunization with gastric mucosa extract. Hyperplasia of enterochromaffin-like (ECL) cells was detected on the 91st day. Antral mucosa remained unchanged.</p><p><strong>Conclusion: </strong>Wistar rats, immunized with gastric mucosa extract, developed EAG similar to human AIG. The advantages of received EAG model are the ease of obtaining, the rapid development of oxyntic mucosa damage, which may progress to ECL cell hyperplasia.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1023-1038"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92153761","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":"High Expression and Significance of Siglec10/CD24 in Unexplained Missed Abortion.","authors":"Hui Lin, Lei Gao, Yu Huang","doi":"10.1080/08820139.2023.2279653","DOIUrl":"10.1080/08820139.2023.2279653","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the expression of Siglec10 and CD24 in normal early pregnancy and missed abortion, and their significance in the maternal-fetal interface.</p><p><strong>Methods: </strong>For our research, we employed Q-PCR and WB techniques to evaluate the traits and expression of Siglec10 and CD24 in the nonpregnant endometrium, as well as in the villus and decidua of women in their 6-10 weeks of normal early pregnancy and those who experienced missed abortion. Additionally, we utilized ELISA to determine the levels of Siglec10 and CD24 in the peripheral blood of pregnancy, missed abortion, and non-pregnant individuals. T-test and ANOVA were used to compare groups.</p><p><strong>Results: </strong>1. Villous tissues in early pregnancy showed high expression of Siglec10 and CD24, with a significant increase in expression in the missed abortion group (<i>P</i> < 0.01).2. Nonpregnant endometrial tissue showed low expression of Siglec10 and CD24, while early pregnancy decidua showed high expression, with even higher expression in missed abortion (all <i>P</i> < 0.05).3. Serum levels of Siglec10 and CD24 in normal early pregnancy were significantly higher than non-pregnancy (<i>P</i> < 0.01). However, the missed abortion group showed significantly higher levels than normal pregnancy (<i>P</i> < 0.01).4. CD24 expression in serum of missed abortion increases with Siglec10 expression, indicating a significant positive correlation (<i>r</i> = 0.500, <i>P</i> < 0.01).</p><p><strong>Conclusion: </strong>Siglec10 and CD24 expression in villus, decidua, and peripheral blood are up-regulated in unexplained missed abortions than those of women with normal pregnancies. This suggests that the levels of serum Siglec10 and CD24 can be used as an effective predictor of missed abortion.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"997-1007"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71481085","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":"Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma.","authors":"Farsaneh Sadeghlar, Julia Seelemann, Annabelle Vogt, Christian Möhring, Taotao Zhou, Robert Mahn, Miroslaw Kornek, Veronika Lukacs-Kornek, Noelia Casares, Juan José Lasarte, Pablo Sarobe, Cornelius van Beekum, Hanno Matthaei, Steffen Manekeller, Jörg Kalff, Ingo G H Schmidt-Wolf, Christian P Strassburg, Maria A Gonzalez-Carmona","doi":"10.1080/08820139.2023.2261980","DOIUrl":"10.1080/08820139.2023.2261980","url":null,"abstract":"<p><strong>Background & aims: </strong>Vaccination with tumor-associated antigen-pulsed dendritic cells leads to specific T-cell response against hepatocellular carcinoma. However, clinical response has been shown to be limited. High regulatory T-cell count is associated with poor prognosis and seems to mediate immune tolerance in hepatocellular carcinoma. Forkhead box P3-peptide inhibitor P60 has been shown to specifically inhibit regulatory T-cell function in murine models. Aim of this study was to investigate whether P60 can improve the immune response induced by vaccination with adenovirus-transduced dendritic cells expressing alpha-fetoprotein in subcutaneous and orthotopic murine models for hepatocellular carcinoma.</p><p><strong>Methods: </strong>Mice developing subcutaneous or orthotopic HCC received daily treatment with P60 starting at different tumor stages. Additionally, mice were vaccinated twice with dendritic cells expressing alpha-fetoprotein.</p><p><strong>Results: </strong>In a preventive setting prior to tumor engraftment, vaccination with alpha-fetoprotein-expressing dendritic cells significantly decreased tumor growth in a subcutaneous model (<i>p</i> = .0256), but no further effects were achieved by addition of P60. However, P60 enhanced the antitumoral effect of a vaccination with alpha-fetoprotein-expressing dendritic cells in established subcutaneous and orthotopic hepatocellular carcinoma characterized by high Treg levels (<i>p</i> = .011).</p><p><strong>Conclusion: </strong>In this study, we showed that vaccination with alpha-fetoprotein-expressing dendritic cells in combination with a specific inhibition of regulatory T-cells by using P60 leads to synergistic tumor inhibition and prolonged survival. This emphasizes the importance of regulatory T-cells inhibition for obtaining an effective antitumoral immune response in hepatocellular carcinoma.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"966-984"},"PeriodicalIF":2.8,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41235002","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":"Genetic and Epigenetic Regulation of the Innate Immune Response to Gout.","authors":"Jordana Dinorá de Lima, André Guilherme Portela de Paula, Bruna Sadae Yuasa, Caio Cesar de Souza Smanioto, Maria Clara da Cruz Silva, Priscila Ianzen Dos Santos, Karin Braun Prado, Angelica Beate Winter Boldt, Tárcio Teodoro Braga","doi":"10.1080/08820139.2023.2168554","DOIUrl":"10.1080/08820139.2023.2168554","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Gout is a disease caused by uric acid (UA) accumulation in the joints, causing inflammation. Two UA forms - monosodium urate (MSU) and soluble uric acid (sUA) have been shown to interact physically with inflammasomes, especially with the nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3), albeit the role of the immune response to UA is poorly understood, given that asymptomatic hyperuricemia does also exist. Macrophage phagocytosis of UA activate NLRP3, lead to cytokines release, and ultimately, lead to chemoattract neutrophils and lymphocytes to the gout flare joint spot. Genetic variants of inflammasome genes and of genes encoding their molecular partners may influence hyperuricemia and gout susceptibility, while also influencing other comorbidities such as metabolic syndrome and cardiovascular diseases. In this review, we summarize the inflammatory responses in acute and chronic gout, specifically focusing on innate immune cell mechanisms and genetic and epigenetic characteristics of participating molecules. Unprecedently, a novel UA binding protein - the neuronal apoptosis inhibitor protein (NAIP) - is suggested as responsible for the asymptomatic hyperuricemia paradox.&lt;b&gt;Abbreviation:&lt;/b&gt; β2-integrins: leukocyte-specific adhesion molecules; ABCG2: ATP-binding cassete family/breast cancer-resistant protein; ACR: American college of rheumatology; AIM2: absent in melanoma 2, type of pattern recognition receptor; ALPK1: alpha-protein kinase 1; ANGPTL2: angiopoietin-like protein 2; ASC: apoptosis-associated speck-like protein; BIR: baculovirus inhibitor of apoptosis protein repeat; BIRC1: baculovirus IAP repeat-containing protein 1; BIRC2: baculoviral IAP repeat-containing protein 2; C5a: complement anaphylatoxin; cAMP: cyclic adenosine monophosphate; CARD: caspase activation and recruitment domains; CARD8: caspase recruitment domain-containing protein 8; CASP1: caspase 1; CCL3: chemokine (C-C motif) ligand 3; CD14: cluster of differentiation 14; CD44: cluster of differentiation 44; Cg05102552: DNA-methylation site, usually cytosine followed by guanine nucleotides; contains arbitrary identification code; CIDEC: cell death-inducing DNA fragmentation factor-like effector family; CKD: chronic kidney disease; CNV: copy number variation; CPT1A: carnitine palmitoyl transferase - type 1a; CXCL1: chemokine (CXC motif) ligand 1; DAMPs: damage associated molecular patterns; DC: dendritic cells; DNMT(1): maintenance DNA methyltransferase; eQTL: expression quantitative trait loci; ERK1: extracellular signal-regulated kinase 1; ERK2: extracellular signal-regulated kinase 2; EULAR: European league against rheumatism; GMCSF: granulocyte-macrophage colony-stimulating factor; GWAS: global wide association studies; H3K27me3: tri-methylation at the 27th lysine residue of the histone h3 protein; H3K4me1: mono-methylation at the 4th lysine residue of the histone h3 protein; H3K4me3: tri-methylation at the 4th lysine residue of the histone h3 prote","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"52 3","pages":"364-397"},"PeriodicalIF":2.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9233546","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":"Association of Killer Cell Immunoglobulin-Like Receptors and Their HLA-Ligands with Type 1 Diabetes Among South Indian Population.","authors":"Nagarajan Gunavathy,&nbsp;Arthur Asirvatham,&nbsp;Ayyappan Chitra,&nbsp;Mariakuttikan Jayalakshmi","doi":"10.1080/08820139.2023.2165940","DOIUrl":"https://doi.org/10.1080/08820139.2023.2165940","url":null,"abstract":"<p><strong>Background: </strong>Type 1 diabetes (T1D) is a multifactorial autoimmune disease, involving strong genetic components with familial predisposition. Killer cell immunoglobulin-like receptors (KIRs) found on the surface of NK cells have ligands of human leukocyte antigen (HLA) class I that are associated with T1D. The present study evaluates the influence of KIR genes and their HLA-ligands in the aetiology of T1D among the South Indian population.</p><p><strong>Methods: </strong>A total of 125 T1D patients, along with their parents (<i>n</i> = 126) and siblings (<i>n</i> = 52) were recruited. PCR-based genotyping was performed for KIR genes and HLA class I ligands. The gene frequencies were compared between patients and siblings/parents. Linkage-disequilibrium (LD) analysis was performed to assess the genetic association between KIR gene pairs.</p><p><strong>Results: </strong>The results show significant differences in HLA-ligands of KIR genes between patients and parents. The HLA-C1C1 homozygosity was found to be a predisposing risk factor, and HLA-C1C2 heterozygosity was protective towards T1D along with either the activating KIR2DS2 or inhibitory KIRs 2DL1, 2DL2, 2DL3. However, the frequency of inhibitory KIR3DL1 significantly increased in the presence of HLA-B Bw4 Ile80 in parents when compared to patients showing a protective effect on T1D. Two pairs of KIR genes, 2DS4-3DL1 and 2DS1-2DL5, showed strong LD in patients, siblings and parents.</p><p><strong>Conclusion: </strong>The KIR-HLA ligand combinations have a significant effect on T1D aetiology among the South Indian population. This study defines a pattern for family-based association studies with genotypic information about KIR genes and their HLA-ligands, providing the first evidence towards T1D among the South Indian population.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"52 3","pages":"270-285"},"PeriodicalIF":2.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9243737","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":"Investigation of IL-35 and IL-39, New Members of the IL-12 Family, in Different Clinical Presentations of Brucellosis.","authors":"Pınar Hız Ellergezen,&nbsp;Muhammed Ali Kizmaz,&nbsp;Abdurrahman Simsek,&nbsp;Nesrin Demir,&nbsp;Eren Cagan,&nbsp;S Haldun Bal,&nbsp;E Halis Akalin,&nbsp;H Barbaros Oral,&nbsp;Ferah Budak","doi":"10.1080/08820139.2023.2165941","DOIUrl":"https://doi.org/10.1080/08820139.2023.2165941","url":null,"abstract":"<p><p>Brucellosis is significantly influenced by the interactions between the causative <i>Brucella</i> bacteria and host immunity. Recently identified cytokines have been described for their immunomodulatory effects in numerous inflammatory, autoimmune and infectious diseases. Some of them are new members of cytokine superfamilies, including several members of the IL-12 superfamily (IL-35, IL-39). The major purpose of the present study was to investigate the role of these new immunomodulatory cytokines in <i>Brucella</i> infections. The levels of IL-35 and IL-39 in the serum of 40 acute and 40 chronic brucellosis patients and 40 healthy controls were measured by ELISA. The mRNA levels of IL-35 and IL-39 in PBMCs were detected by RT-qPCR. Both IL-35 and IL-39 serum concentrations were significantly higher in healthy control subjects than in brucellosis patients, and IL-35 and IL-39 serum levels of chronic brucellosis patients were higher than those of acute cases. It was also found that the expression of Ebi3/IL-12A (IL-35 genes) and Ebi3/IL-23A (IL-39 genes) was upregulated in chronic brucellosis patients compared to healthy controls. Moreover, the expression of the Ebi3/IL-12A and Ebi3/IL-23A genes was lower in patients with acute brucellosis than in patients with chronic brucellosis. Overall, this study showed that IL-35 and IL-39 are positively correlated in brucellosis and significantly decreased during the disease. Significantly lower levels of IL-35 and IL-39 in acute brucellosis than in chronic brucellosis and healthy controls suggest that these cytokines may play a key role in suppressing the immune response to brucellosis and its progression to chronicity.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":"52 3","pages":"286-297"},"PeriodicalIF":2.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9591277","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}