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https://www.readbyqxmd.com/read/28213589/sh479-a-betulinic-acid-derivative-ameliorates-experimental-autoimmune-encephalomyelitis-by-regulating-the-th17-treg-balance
#1
Jing Li, Ji Jing, Yang Bai, Zhen Li, Roumei Xing, Binhe Tan, Xueyun Ma, Wenwei Qiu, Changsheng Du, Bing Du, Fan Yang, Jie Tang, Stefan Siwko, Mingyao Liu, Huaqing Chen, Jian Luo
CD4+ T helper cells, especially Th17 cells, combined with immune regulatory network dysfunction, play key roles in autoimmune diseases including multiple sclerosis (MS). Betulinic acid (BA), a natural pentacyclic triterpenoid, has been reported to be involved in anti-inflammation, in particular having an inhibitory effect on pro-inflammatory cytokine IL-17 and IFN-γ production. In this study, we screened BA derivatives and found a BA derivative, SH479, which had a greater inhibitory effect on Th17 differentiation...
February 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28212864/gpr43-activation-enhances-psoriasis-like-inflammation-through-epidermal-upregulation-of-il-6-and-dual-oxidase-2-signaling-in-a-murine-model
#2
Ahmed Nadeem, Sheikh F Ahmad, Naif O Al-Harbi, Ahmed M El-Sherbeeny, Mohammed M Al-Harbi, Talal S Almukhlafi
The gut is densely inhabited by commensal bacteria, which metabolize dietary fibers/undigested carbohydrates and produce short-chain fatty acids such as acetate. GPR43 is one of the receptors to sense short-chain fatty acids, and expressed in various immune and non-immune cells. Acetate/GPR43 signaling has been shown to affect various inflammatory diseases through Th17 responses and NADPH oxidase (NOX)-derived reactive oxygen species (ROS) generation. However, no study has previously explored the effects of GPR43 activation during psoriasis-like inflammation...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28212793/mir-634-is-a-pol-iii-dependent-intronic-microrna-regulating-alternative-polyadenylated-isoforms-of-its-host-gene-prkca
#3
Elvezia Maria Paraboschi, Giulia Cardamone, Valeria Rimoldi, Stefano Duga, Giulia Soldà, Rosanna Asselta
BACKGROUND: The protein kinase C alpha (PRKCA) gene, coding for a Th17-cell-selective kinase, shows a complex splicing pattern, with at least 2 stable alternative transcripts characterized by an alternative upstream polyadenylation site. Polymorphisms in this gene were associated with several conditions, including multiple sclerosis, asthma, schizophrenia, and cancer. The presence of a microRNA (miRNA), i.e. miR-634, within intron 15 of the PRKCA gene, suggests the intriguing possibility that this miRNA might play a role in the susceptibility to these pathologies...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212158/an-integrated-understanding-of-the-immunology-of-allograft-inflammation
#4
Brenna Houlihan, Priscilla Cha, Michael Zasloff, Thomas M Fishbein, Alexander Kroemer
PURPOSE OF REVIEW: The purpose of this review is to summarize recent advances in our understanding of the complex immunology of intestinal transplantation and allograft rejection. RECENT FINDINGS: Recent findings highlight the importance of the intestinal microbiome for intestinal homeostasis and the role of newly discovered innate lymphoid cells in intestinal transplantation. In addition, the role of host antimicrobial Th17 responses in the pathogenesis of inflammatory bowel diseases and intestinal allograft rejection has been further elucidated...
February 15, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28210632/increased-interleukin-17f-is-associated-with-elevated-autoantibody-levels-and-more-clinically-relevant-than-interleukin-17a-in-primary-sj%C3%A3-gren-s-syndrome
#5
Yuzhou Gan, Xiaozhen Zhao, Jing He, Xu Liu, Yun Li, Xiaolin Sun, Zhanguo Li
Th17 related immune response is pathogenic in primary Sjögren's syndrome (pSS). However, the role of IL-17F, one potent inflammatory member of IL-17 family cytokines in pSS, has not been specifically defined. We recruited one hundred and nine pSS patients and forty-two healthy controls and their serum levels of IL-17A and IL-17F were determined by multiplex cytokine assays. White blood cell, red blood cell, neutrophil, lymphocyte, IgM, IgG, C3, C4, RF, ANA, anti-SSA antibody, and anti-SSB antibody were measured by standard laboratory techniques...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28209777/cd6-as-a-potential-target-for-treating-multiple-sclerosis
#6
Yan Li, Nora G Singer, Joy Whitbred, Michael A Bowen, David A Fox, Feng Lin
CD6 was established as a marker of T cells more than three decades ago, and recent studies have identified CD6 as a risk gene for multiple sclerosis (MS), a disease in which autoreactive T cells are integrally involved. Nevertheless, the precise role of CD6 in regulating T-cell responses is controversial and its significance in the pathogenesis of various diseases remains elusive, partly due to the lack of animals engineered to alter expression of the CD6 gene. In this report, we found that CD6 KO mice showed decreased pathogenic T-cell responses, reduced spinal cord T-cell infiltration, and attenuated disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28207945/cd4-cd25-garp-tregs-display-a-compromised-suppressive-function-in-patients-with-dilated-cardiomyopathy
#7
Yuzhen Wei, Kunwu Yu, Hui Wei, Xin Su, Ruirui Zhu, Huairui Shi, Haitao Sun, Quan Luo, Wenbin Xu, Junhui Xiao, Yucheng Zhong, Qiutang Zeng
Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein -A repetitions predominant (GARP) expressed on activated CD4(+) T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4(+) CD25(+) GARP(+) regulatory T cells (Tregs) in DCM. 45 DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral Th1 and Th17 number and their related cytokines (IFN-γ, IL-17), and an obvious decrease in Treg number, TGF-β1 levels and the expression of FOXP3 and GARP in patients with DCM as compared with controls...
February 16, 2017: Immunology
https://www.readbyqxmd.com/read/28207936/th17-cells-and-neutrophils-close-collaborators-in-chronic-leishmania-mexicana-infections-leading-to-disease-severity
#8
Claudia Patricia Pedraza-Zamora, José Delgado-Domínguez, Jaime Zamora-Chimal, Ingeborg Becker
Cutaneous leishmaniasis caused by Leishmania mexicana is associated with an important inflammatory response. We here analyzed the kinetics of Th17 cells and neutrophils in earlobe lesions caused by Leishmania mexicana throughout 90 days of disease progresion in susceptible BALB/c and semi-resistant C57BL/6 mice infected with 1x10(5) Leishmania mexicana promastigotes. Cells in the lesions were extracted and quantified by flow cytometry, whereas their distribution in the tissues in relation to the parasites was analyzed by immunohistochemistry...
February 16, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28207428/il-37-ameliorates-coxsackievirus-b3-induced-viral-myocarditis-by-modulating-the-th17-treg-immune-response
#9
Bang An, Xuefei Liu, Ge Li, Haitao Yuan
Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle with an excessively activated immune response. Numerous interventions have been investigated for the treatment of myocarditis while success is limited. Interleukin-37 (IL-37), a novel member of the IL-1 cytokine family, is a natural inhibitor of innate immunity associated with autoimmune diseases. However, the modulatory effect of IL-37 in myocarditis is unknown. In this study, we investigated the immunological regulation of IL-37 in the coxsackievirus B3-induced model of murine viral myocarditis...
February 14, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28203226/microbial-anti-inflammatory-molecule-mam-from-faecalibacterium-prausnitzii-shows-a-protective-effect-on-dnbs-and-dss-induced-colitis-model-in-mice-through-inhibition-of-nf-%C3%AE%C2%BAb-pathway
#10
Natalia M Breyner, Cristophe Michon, Cassiana S de Sousa, Priscilla B Vilas Boas, Florian Chain, Vasco A Azevedo, Philippe Langella, Jean M Chatel
Faecalibacterium prausnitzii and its supernatant showed protective effects in different chemically-induced colitis models in mice. Recently, we described 7 peptides found in the F. prausnitzii supernatant, all belonging to a protein called Microbial Anti-inflammatory Molecule (MAM). These peptides were able to inhibit NF-κB pathway in vitro and showed anti-inflammatory properties in vivo in a DiNitroBenzene Sulfate (DNBS)-induced colitis model. In this current proof we tested MAM effect on NF-κB pathway in vivo, using a transgenic model of mice producing luciferase under the control of NF-κB promoter...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28202908/silencing-c-rel-in-macrophages-dampens-th1-and-th17-immune-responses-and-alleviates-experimental-autoimmune-encephalomyelitis-in-mice
#11
Hongling Zhang, Jiacheng Bi, Huqiang Yi, Tingting Fan, Qingguo Ruan, Lintao Cai, Youhai H Chen, Xiaochun Wan
Autoimmune Th1 and Th17 responses are critical for the development of central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Although macrophages play important roles in the development of Th1 and Th17 responses, whether modulating macrophage gene transcription can diminish Th1- and Th17 cell-induced CNS pathology is unclear. In this study, we successfully silenced the expression of the transcription factor c-Rel in macrophages of mice with EAE (including those infiltrating the CNS) using chemically modified c-Rel-specific siRNAs delivered by nanoparticles...
February 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28202745/plasma-levels-of-eicosapentaenoic-acid-are-associated-with-anti-tnf-responsiveness-in-rheumatoid-arthritis-and-inhibit-the-etanercept-driven-rise-in-th17-cell-differentiation-in-vitro
#12
Louisa Jeffery, Helena L Fisk, Philip C Calder, Andrew Filer, Karim Raza, Christopher D Buckley, Iain McInnes, Peter C Taylor, Benjamin A Fisher
OBJECTIVE: To determine whether levels of plasma n-3 polyunsaturated fatty acids are associated with response to antitumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA), and whether this putative effect may have its basis in altering anti-TNF-driven Th17 cell differentiation. METHODS: Plasma was collected at baseline and after 3 months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component was measured...
February 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28201637/reduced-th17-responses-to-streptococcus-pneumoniae-in-infection-prone-children-can-be-rescued-by-addition-of-innate-cytokines
#13
Saleem Basha, Ravinder Kaur, Tim R Mosmann, Michael E Pichichero
No abstract text is available yet for this article.
February 13, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28198424/human-ido-competent-long-lived-immunoregulatory-dendritic-cells-induced-by-intracellular-pathogen-and-their-fate-in-humanized-mice
#14
Rajeev K Tyagi, Brodie Miles, Rajesh Parmar, Neeraj K Garg, Sarat K Dalai, Babak Baban, Christopher W Cutler
Targeting of myeloid-dendritic cell receptor DC-SIGN by numerous chronic infectious agents, including Porphyromonas gingivalis, is shown to drive-differentiation of monocytes into dysfunctional mDCs. These mDCs exhibit alterations of their fine-tuned homeostatic function and contribute to dysregulated immune-responses. Here, we utilize P. gingivalis mutant strains to show that pathogen-differentiated mDCs from primary human-monocytes display anti-apoptotic profile, exhibited by elevated phosphorylated-Foxo1, phosphorylated-Akt1, and decreased Bim-expression...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198408/therapeutic-effects-of-human-adipose-tissue-derived-stem-cell-hadsc-transplantation-on-experimental-autoimmune-encephalomyelitis-eae-mice
#15
Jia Li, Ying Chen, Zhibo Chen, Yuanyuan Huang, Dehao Yang, Zhongqian Su, Yiyun Weng, Xiang Li, Xu Zhang
This study is to investigate the therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. EAE mouse model was established by MOG35-55 immunization. Body weight and neurological function were assessed. H&E and LFB staining was performed to evaluate histopathological changes. Flow cytometry was used to detect Th17 and Treg cells. ELISA and real-time PCR were performed to determine transcription factor and pro-inflammatory cytokine levels...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198366/th17-cells-express-st2-and-are-controlled-by-the-alarmin-il-33-in-the-small-intestine
#16
A Pascual-Reguant, J Bayat Sarmadi, C Baumann, R Noster, D Cirera-Salinas, C Curato, P Pelczar, S Huber, C E Zielinski, M Löhning, A E Hauser, E Esplugues
TH17 cells are major drivers of inflammation and involved in several autoimmune diseases. Tissue inflammation is a beneficial host response to infection, but it can also contribute to autoimmunity. The crosstalk between a tissue and the immune system during an inflammatory response is key for preserving tissue integrity and restoring physiological processes. However, how the inflamed tissue regulates the magnitude of an immune response by controlling pro-inflammatory T cells is not well characterized so far...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28198034/human-th17-migration-in-three-dimensional-collagen-involves-p38-mapk
#17
Maleck Kadiri, Mohamed-Amine El Azreq, Sofiane Berrazouane, Marc Boisvert, Fawzi Aoudjit
T cell migration across extracellular matrix (ECM) is an important step of the adaptive immune response but is also involved in the development of inflammatory autoimmune diseases. Currently, the molecular mechanisms regulating the motility of effector T cells in ECM are not fully understood. Activation of p38 MAPK has been implicated in T cell activation and is critical to the development of immune and inflammatory responses. In this study, we examined the implication of p38 MAPK in regulating the migration of human Th17 cells through collagen...
February 15, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28197386/deficiency-of-the-immunostimulatory-cytokine-il-21-promotes-intestinal-neoplasia-via-dysregulation-of-the-th1-th17-axis
#18
Mia Shapiro, Bisweswar Nandi, Gabriel Gonzalez, Rao H Prabhala, Hiroshi Mashimo, Qin Huang, Natasha Y Frank, Nikhil C Munshi, Jason S Gold
IL-21 has reported activity in promoting both Th1 and Th17 immune responses. Its role in sporadic human colorectal cancer is unknown. We aimed to delineate the role of IL-21 in a model of sporadic intestinal carcinogenesis. We found that in APC(MIN/+) mice, ablation of IL-21 increased intestinal tumorigenesis. Expression of pro-inflammatory Th17-associated genes, including RORγt and IL-17A, was increased in the intestine in the absence of IL-21, while expression of antitumor Th1-associated genes Tbet, IFNγ, granzyme B, and perforin was decreased...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196884/functional-genomics-analysis-of-vitamin-d-effects-on-cd4-t-cells-in-vivo-in-experimental-autoimmune-encephalomyelitis-%C3%A2
#19
Manuel Zeitelhofer, Milena Z Adzemovic, David Gomez-Cabrero, Petra Bergman, Sonja Hochmeister, Marie N'diaye, Atul Paulson, Sabrina Ruhrmann, Malin Almgren, Jesper N Tegnér, Tomas J Ekström, André Ortlieb Guerreiro-Cacais, Maja Jagodic
Vitamin D exerts multiple immunomodulatory functions and has been implicated in the etiology and treatment of several autoimmune diseases, including multiple sclerosis (MS). We have previously reported that in juvenile/adolescent rats, vitamin D supplementation protects from experimental autoimmune encephalomyelitis (EAE), a model of MS. Here we demonstrate that this protective effect associates with decreased proliferation of CD4+ T cells and lower frequency of pathogenic T helper (Th) 17 cells. Using transcriptome, methylome, and pathway analyses in CD4+ T cells, we show that vitamin D affects multiple signaling and metabolic pathways critical for T-cell activation and differentiation into Th1 and Th17 subsets in vivo...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28195151/in-patients-with-chronic-aplastic-anemia-bone-marrow-derived-mscs-regulate-the-treg-th17-balance-by-influencing-the-notch-rbp-j-foxp3-ror%C3%AE-t-pathway
#20
Hongbo Li, Lin Wang, Yan Pang, Zujun Jiang, Zenghui Liu, Haowen Xiao, Haijia Chen, Xiaohu Ge, Hai Lan, Yang Xiao
The standard treatment for aplastic anemia (AA) in young patients is a matched sibling hematopoietic stem cell transplant. Transfusion of a chronic AA patient with allogeneic bone marrow-derived mesenchymal stromal cells (BMMSCs) is currently being developed as a cell-based therapy, and the safety and efficacy of such transfusions are being continuously improved. Nevertheless, the mechanisms by which BMMSCs exert their therapeutic effects remain to be elucidated. In this study, mesenchymal stromal cells (MSCs) obtained from bone marrow donors were concentrated and intravenously injected into 15 chronic AA patients who had been refractory to prior immunosuppressive therapy...
February 14, 2017: Scientific Reports
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