المؤلفون: Wei, Yankai, Yang, Chao, Liu, Yuling, Sun, Deming, Li, Xiaorong, Wei, Ruihua, Nian, Hong

المصدر: The FASEB Journal. 37(11)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Immunology, Autoimmune Disease, Biotechnology, Prevention, Biodefense, Eye Disease and Disorders of Vision, Vaccine Related, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Animals, Th17 Cells, Autoimmune Diseases, Methyltransferases, p38 Mitogen-Activated Protein Kinases, Uveitis, Dendritic Cells, MicroRNAs, Dusp16, Mettl3, Th17 cell, dendritic cells, miR-338-3p, p38 signaling, Biochemistry and Cell Biology, Physiology, Medical Physiology, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical physiology

الوصف: Pathogenic Th17 cells are critical drivers of multiple autoimmune diseases, including uveitis and its animal model, experimental autoimmune uveitis (EAU). However, how innate immune signals modulate pathogenic Th17 responses remains largely unknown. Here, we showed that miR-338-3p endowed dendritic cells (DCs) with an increased ability to activate interphotoreceptor retinoid-binding protein (IRBP)1-20 -specific Th17 cells by promoting the production of IL-6, IL-1β, and IL-23. In vivo administration of LV-miR-338-infected DCs promoted pathogenic Th17 responses and exacerbated EAU development. Mechanistically, dual-specificity phosphatase 16 (Dusp16) was a molecular target of miR-338-3p. miR-338-3p repressed Dusp16 and therefore strengthened the mitogen-activated protein kinase (MAPK) p38 signaling, resulting in increased production of Th17-polarizing cytokines and subsequent pathogenic Th17 responses. In addition, methyltransferase like 3 (Mettl3), a key m6A methyltransferase, mediated the upregulation of miR-338-3p in activated DCs. Together, our findings identify a vital role for Mettl3/miR-338-3p/Dusp16/p38 signaling in DCs-driven pathogenic Th17 responses and suggest a potential therapeutic avenue for uveitis and other Th17 cell-related autoimmune disorders.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8md7z134Test

المؤلفون: Rabe, Hardis, Lönnermark, Elisabeth, Johansson, Ewa, Gilljam, Marita, Jönsson, Bodil

المصدر: Tuberculosis. 147

مصطلحات موضوعية: BCG vaccine, cytokine, gamma interferon, interleukin 10, interleukin 12p70, interleukin 17, interleukin 22, interleukin 23, interleukin 23p19, interleukin 23p40, tuberculin, unclassified drug, adolescent, adult, aged, Article, atypical mycobacteriosis, atypical Mycobacterium, bacterial strain, BCG vaccination, cell culture, cell isolation, clinical article, commensal Escherichia coli, comparative study, controlled study, cystic fibrosis, cytokine production, cytokine response, density gradient centrifugation, Enterococcus faecalis, enzyme linked immunosorbent assay, female, homozygote, human, human cell, in vitro study, laboratory, latent tuberculosis, limit of detection, male, Mycobacterium abscessus subsp. abscessus, Mycobacterium avium, Mycobacterium gordonae, Mycobacterium massiliense, nonhuman, peripheral blood mononuclear cell, Pseudomonas aeruginosa, stimulation, Streptococcus mitis, supernatant, Th17 cell, tuberculin test, tuberculosis, viable cell count

الوصف: Mycobacterium tuberculosis and opportunistic environmental non-tuberculous mycobacteria (NTM) can cause severe infection. Why latent tuberculosis infection advances to active disease, and why some individuals with cystic fibrosis (CF) develop pulmonary infections with NTM is still poorly understood. The aim of this study was to investigate the effector function of peripheral blood mononuclear cells (PBMC) from individuals with active or latent tuberculosis, individuals with CF with or without pulmonary NTM-infection and healthy controls, by measuring cytokine response to in vitro stimulation with different species of NTMs. The cytokine concentrations of IL-17A, IL-22, IL-23, IL-10, IL12p70 and IFN-γ were measured in PBMC-culture supernatants after stimulation with NTMs. PBMCs from individuals with latent tuberculosis infection showed strong IL-17A, IL-22, and IFN-γ responses compared to individuals with active tuberculosis or CF. IL-10 production was low in both tuberculosis groups compared to the CF groups and controls. This study suggests that IL-17A and IL-22 might be important to keep tuberculosis in a latent phase and that individuals with CF with an ongoing NTM infection seem to have a low cytokine response. © 2024 The Authors

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:ri:diva-72802Test
https://doi.org/10.1016/j.tube.2024.102504Test
https://ri.diva-portal.org/smash/get/diva2:1857798/FULLTEXT01.pdfTest

المؤلفون: Lanjiao Li, Jichun Chen, Zhenyan Wang, Yan Xu, Hao Yao, Wulong Lei, Xiyuan Zhou, Minming Zheng

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: NECA, diabetic retinopathy, dendritic cells, toll-like receptor, Treg cell, Th17 cell, Immunologic diseases. Allergy, RC581-607

الوصف: IntroductionThis study examined the impact of 5’-(N- ethylcarboxamido)adenosine (NECA) in the peripheral blood of healthy individuals, those with diabetes mellitus, diabetic retinopathy (DR), and C57BL/6 mice, both in vivo and in vitro.MethodsEnzyme-linked immunosorbent assay (ELISA) and flow cytometry (FCM) were used to evaluate the effects of NECA on dendritic cells (DCs) and mouse bone marrow-derived dendritic cells (BMDCs) and the effects of NECA-treated DCs on Treg and Th17 cells. The effect of NECA on the Toll-like receptor (TLR) pathway in DCs was evaluated using polymerase chain reaction (PCR) and western blotting (WB).ResultsFCM and ELISA showed that NECA inhibited the expression of surface markers of DCs and BMDCs, increased anti-inflammatory cytokines and decreased proinflammatory cytokines. PCR and WB showed that NCEA decreased mRNA transcription and protein expression in the TLR-4-MyD88-NF-kβ pathway in DCs and BMDCs. The DR severity in streptozocin (STZ) induced diabetic mice was alleviated. NECA-treated DCs and BMDCs were co-cultivated with CD4+T cells, resulting in modulation of Treg and Th17 differentiation, along with cytokine secretion alterations.ConclusionNECA could impair DCs’ ability to present antigens and mitigate the inflammatory response, thereby alleviating the severity of DR.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1415004/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/1a6a9a72bd0646e69e15df914eab2b18Test

المؤلفون: Tsai Sen-Wei, Wang Jou-Hsuan, Chang Yu-Kang, Lin Chi-Chen

المصدر: Open Life Sciences, Vol 18, Iss 1, Pp 1233-40 (2023)

مصطلحات موضوعية: rheumatoid arthritis, collagen-induced arthritis, th17 cell, erianin, natural compound, inflammation, Biology (General), QH301-705.5

الوصف: Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Its pathogenesis is complicated but highly related to aberrant Th17 overactivation. Uncontrolled Th17 cell expansion and activation in populations and associated activities contribute to the progression of RA. Although clinical RA remedies are available, not all RA patients respond to these treatments, and adverse effects are always a concerning issue during treatment. To expand the repertoire of possible anti-RA remedies, we chose the phytochemical compound erianin, isolated from Dendrobium sp., and evaluated its antiarthritic effect in vitro and in vivo. We found that erianin efficiently controlled the differentiation and activation of Th17 cell development from primary CD4 T cells, limiting IL-17A cytokine production and RORγT transcript generation. In line with molecular docking models, the essential signaling pathway for Th17 polarization, the JAK/STAT3 pathway, was inhibited upon erianin treatment, with dose-dependent inhibition of phosphorylation shown by western blotting. More importantly, erianin treatment reduced arthritic manifestations and proinflammatory cytokine levels in collagen-induced arthritis (CIA) mice, as well as protecting the joint histological microstructure. Overall, erianin revealed a promising inhibitory effect on Th17 overactivation and decreased disability in CIA mice. Therefore, erianin could be further developed as a candidate RA remedy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2391-5412Test

الوصول الحر: https://doaj.org/article/0098f619613840bbb635288189a01f49Test

المؤلفون: CHEN Yuting, HUANG Ling, XIA Junjie, QIU Yu, YI Ke, WANG Jincheng

المصدر: Jichu yixue yu linchuang, Vol 43, Iss 8, Pp 1322-1325 (2023)

مصطلحات موضوعية: t-bet, th1 cell, th2 cell, th17 cell, chronic obstructive pulmonary disease, Medicine

الوصف: Chronic obstructive pulmonary disease (COPD) is a chronic and progressive respiratory disease. Transcription factor T-bet is involved in the inflammatory response and lung function changes of COPD, which is expected to become a new target for the prevention and treatment of COPD. It might provide a new idea for the targeted research of COPD.

وصف الملف: electronic resource

العلاقة: http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/1001-6325-2023-43-8-1322.pdfTest; https://doaj.org/toc/1001-6325Test

الوصول الحر: https://doaj.org/article/b65a953d576d47cd89b9b353d4883545Test

المؤلفون: Han, Kim, Singh, Komudi, Meadows, Allison M., Sharma, Rahul, Hassanzadeh, Shahin, Wu, Jing, Goss-Holmes, Haley, Huffstutler, Rebecca D., Teague, Heather L., Mehta, Nehal N., Griffin, Julian L., Tian, Rong, Traba Domínguez, Javier, Sack, Michael N.

مصطلحات موضوعية: arginine biosynthesis, NAD boosting +, nicotinamide riboside, CD4 T cell +, nrf2, Th17 cell, psoriasis, Medicina

الوصف: To evaluate whether nicotinamide adenine dinucleotide-positive (NAD+) boosting modulates adaptive immunity, primary CD4+ T cells from healthy control and psoriasis subjects were exposed to vehicle or nicotinamide riboside (NR) supplementation. NR blunts interferon γ (IFNγ) and interleukin (IL)-17 secretion with greater effects on T helper (Th) 17 polarization. RNA sequencing (RNA-seq) analysis implicates NR blunting of sequestosome 1 (sqstm1/p62)-coupled oxidative stress. NR administration increases sqstm1 and reduces reactive oxygen species (ROS) levels. Furthermore, NR activates nuclear factor erythroid 2-related factor 2 (Nrf2), and genetic knockdown of nrf2 and the Nrf2-dependent gene, sqstm1, diminishes NR amelioratory effects. Metabolomics analysis identifies that NAD+ boosting increases arginine and fumarate biosynthesis, and genetic knockdown of argininosuccinate lyase ameliorates NR effects on IL-17 production. Hence NR via amino acid metabolites orchestrates Nrf2 activation, augments CD4+ T cell antioxidant defenses, and attenuates Th17 responsiveness. Oral NR supplementation in healthy volunteers similarly increases serum arginine, sqstm1, and antioxidant enzyme gene expression and blunts Th17 immune responsiveness, supporting evaluation of NAD+ boosting in CD4+ T cell-linked inflammation

وصف الملف: application/pdf

العلاقة: Cell Reports Medicine; https://doi.org/10.1016/j.xcrm.2023.101157Test; Gobierno de España. PID2019-105665RA-I00; Cell Reports Medicine 4.9 (2023): 101157; http://hdl.handle.net/10486/711929Test; 101157-1; 101157-24

الإتاحة: https://doi.org/10.1016/j.xcrm.2023.101157Test
http://hdl.handle.net/10486/711929Test

المؤلفون: Ouyang, Kelsey, Oparaugo, Nicole, Nelson, Amanda M, Agak, George W

مصطلحات موضوعية: Biological Sciences, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, Autoimmune Disease, Aetiology, 2.1 Biological and endogenous factors, Infection, Skin, Inflammatory and immune system, Acne Vulgaris, Extracellular Traps, Humans, Propionibacterium acnes, T-Lymphocytes, T cell extracellular traps, acne, Cutibacterium acnes, T(H)17 cell, skin, TH17 cell, Medical Microbiology, Biochemistry and cell biology, Genetics

الوصف: The role of extracellular traps (ETs) in the innate immune response against pathogens is well established. ETs were first identified in neutrophils and have since been identified in several other immune cells. Although the mechanistic details are not yet fully understood, recent reports have described antigen-specific T cells producing T cell extracellular traps (TETs). Depending on their location within the cutaneous environment, TETs may be beneficial to the host by their ability to limit the spread of pathogens and provide protection against damage to body tissues, and promote early wound healing and degradation of inflammatory mediators, leading to the resolution of inflammatory responses within the skin. However, ETs have also been associated with worse disease outcomes. Here, we consider host-microbe ET interactions by highlighting how cutaneous T cell-derived ETs aid in orchestrating host immune responses against Cutibacterium acnes (C. acnes), a commensal skin bacterium that contributes to skin health, but is also associated with acne vulgaris and surgical infections following joint-replacement procedures. Insights on the role of the skin microbes in regulating T cell ET formation have broad implications not only in novel probiotic design for acne treatment, but also in the treatment for other chronic inflammatory skin disorders and autoimmune diseases.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/0540x05cTest

المؤلفون: Susmita Srivastava, Mahaboobkhan Rasool

المصدر: Bangladesh Journal of Pharmacology, Vol 18, Iss 4 (2023)

مصطلحات موضوعية: T helper 17 (Th17) cell, osteoclastogenesis, CYT387, IL-6 trans-signaling, janus kinases, rheumatoid arthritis, Therapeutics. Pharmacology, RM1-950

الوصف: The present study was conducted to investigate the therapeutic efficacy of CYT387 in rheumatoid arthritis pathogenesis concerning T helper 17 cell/regulatory T cell (Th17/Treg) imbalance and osteoclastogenesis. In this study, CYT 387 inhibited the proliferation of Th17 cells and collectively relocated FoxP3 + Treg cell differentiation in vitro. CYT387 mitigated the secretion of pathogenic IL-17 via reduced ROR-γt expression and restored the elevated expression of IL-10 by increasing FOXP3 activity. Alternatively, CYT387 abrogated RANKL expression and significantly increased osteoprotegerin levels by reducing SOX-5 activity. Furthermore, in a co-culture system of IL-6 and sIL-6R stimulated adjuvant-induced arthritic fibroblast-like synoviocytes and monocytes/macrophages collected from rat bone marrow, CYT387 reduced osteoclast formation and bone resorptive activity. In conclusion, CYT387 modulated IL-6/sIL-6R dependent JAK1/STAT3 activation and signaling mechanisms in CD4+T cells under Th17 differentiation conditions and osteoclast cells via dampened activation of SOX-5.

وصف الملف: electronic resource

العلاقة: https://www.banglajol.info/index.php/BJP/article/view/68901Test; https://doaj.org/toc/1991-0088Test

الوصول الحر: https://doaj.org/article/da521fec68b946a4ae60a9274026d128Test

المؤلفون: Ge G, Shang J, Gan T, Chen Z, Pan C, Mei Y, Long S, Wu A, Wang H

المصدر: Journal of Inflammation Research, Vol Volume 16, Pp 2521-2533 (2023)

مصطلحات موضوعية: psoriasis, leprosy, th17 cell, macrophage, il-17a, clec4e, Pathology, RB1-214, Therapeutics. Pharmacology, RM1-950

الوصف: Gai Ge,1 Jingzhe Shang,2,3 Tian Gan,1 Zhiming Chen,1 Chun Pan,1 Youming Mei,1 Siyu Long,4 Aiping Wu,2,3 Hongsheng Wang1,5,6 1Laboratory of Mycobacteria, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, People’s Republic of China; 2Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Suzhou Institute of Systems Medicine, Suzhou, People’s Republic of China; 4Department of Dermatology, Beijing Chao-Yang Hospital & Capital Medical University, Beijing, People’s Republic of China; 5National Center for Sexually Transmitted Disease and Leprosy Control, China Centers for Disease Control and Prevention, Nanjing, People’s Republic of China; 6Centre for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Hongsheng Wang, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 12 Jiang-wang-miao Street, Nanjing, Jiangsu Province, People’s Republic of China, Tel/Fax +86 258 5478953, Email whs33@vip.sina.comPurpose: Psoriasis (Ps) and leprosy are chronic inflammatory skin disorders, characterised by enhanced innate and adaptive immunity. Ps and leprosy rarely coexist. The molecular immune mechanism of the Ps and leprosy rarely coexistence is unclear.Patients and Methods: RNA-sequencing (RNA-seq) was performed on 20 patients with Ps, 5 adults with lepromatous leprosy (L-lep), and 5 patients with tuberculoid leprosy (T-lep) to analyse the differentially expressed genes (DEGs) between them. Moreover, the biological mechanism of Ps and leprosy was explored by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Gene Ontology (GO) analysis, Gene Set Enrichment Analysis analysis, and protein–protein interaction (PPI) analyses. Finally, 13 DEGs of 10 skin biopsies of Ps patients, 6 samples of L-lep patients, 6 samples of T-lep patients and 5 healthy controls were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR).Results: The PPI network was constructed and primarily associated with immune response, IL-17 signalling, and Toll-like receptor pathway between Ps and leprosy. Th17 markers (interleukin (IL)- 19, IL-20, IL-36A, IL-36G, IL-22, IL-17A, and lipocalin-2 (LCN2) had higher expression in Ps than in L-lep and T-lep, whereas macrophage biomarkers (CLEC4E and TREM2), SPP1, and dendritic cell (DC)-related hallmarks (ITGAX) and TNF-a had significantly lower expression across Ps and T-lep than in L-lep.Conclusion: To put it simply, Ps patients with IL-17A, IL-19, IL-20, IL-36A, IL-36G, and IL-22 in conjunction with LCN2 with up-graduated expression might be not susceptible to L-lep. However, high levels of CLEC4E, TREM2, and SPP1 in L-lep patients indicated that they unlikely suffered from Ps.Keywords: psoriasis, leprosy, Th17 cell, macrophage, IL-17A, CLEC4E

وصف الملف: electronic resource

العلاقة: https://www.dovepress.com/psoriasis-and-leprosy-an-arcane-relationship-peer-reviewed-fulltext-article-JIRTest; https://doaj.org/toc/1178-7031Test

الوصول الحر: https://doaj.org/article/d46d6bcd77144defa52facc40f870ec2Test

المؤلفون: Li-Li Wu, Xiao-Yan Li, Kai Deng, Bing-Liang Lin, Hong Deng, Dong-Ying Xie, Geng-Lin Zhang, Qi-Yi Zhao, Zhi-Shuo Mo, Yue-Hua Huang, Zhi-Liang Gao

المصدر: Liver Research, Vol 7, Iss 2, Pp 136-144 (2023)

مصطلحات موضوعية: Chronic hepatitis B (CHB), T helper 17 (Th17) cell, Regulatory T (Treg) cell, Hepatitis B surface antigen (HBsAg) loss, Clinical cure, Pegylated interferon (PEG-IFN), Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: Background and aims: The primary goal of chronic hepatitis B (CHB) treatment is to reduce hepatitis B surface antigen (HBsAg). T helper 17 (Th17) and regulatory T (Treg) cells are essential for the development of CHB. However, how Th17 and Treg cells contribute to HBsAg loss is still unknown. Therefore, this study aimed to search for the predictive value of Th17 and Treg cells for HBsAg loss in CHB patients with low HBsAg quantification. Methods: The study included 99 hepatitis B e antigen (HBeAg)-negative CHB patients who had completed a year of nucleos(t)ide analogue (NA) monotherapy and had received both NA and pegylated interferon (PEG-IFN) treatment for less than 96 weeks (96 wk). In the cured group, 48 patients lost HBsAg within 48 wk, while 51 patients did not (uncured group). Blood samples and clinical data were collected for research. Results: During PEG-IFN and NA combination therapy, the proportion of Th17 cells in the cured group increased significantly, while the proportion of Treg cells in the uncured group increased. From 0 to 24 wk, the proportion of Th17 cells in the cured group was significantly higher than in the uncured group, while the opposite was true for Treg cells. Patients with alanine aminotransferase (ALT) ≥ 2.5 upper limit of normal (ULN) at 12 wk had a higher proportion of Th17 cells and a lower proportion of Treg cells than those with ALT

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2542568423000181Test; https://doaj.org/toc/2542-5684Test

الوصول الحر: https://doaj.org/article/8d959db95e01445fb794174860636754Test