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https://www.readbyqxmd.com/read/29666259/shared-epitope-aryl-hydrocarbon-receptor-crosstalk-underlies-the-mechanism-of-gene-environment-interaction-in-autoimmune-arthritis
#1
Jiaqi Fu, Sarah V Nogueira, Vincent van Drongelen, Patrick Coit, Song Ling, Edward F Rosloniec, Amr H Sawalha, Joseph Holoshitz
The susceptibility to autoimmune diseases is affected by genetic and environmental factors. In rheumatoid arthritis (RA), the shared epitope (SE), a five-amino acid sequence motif encoded by RA-associated HLA-DRB1 alleles, is the single most significant genetic risk factor. The risk conferred by the SE is increased in a multiplicative way by exposure to various environmental pollutants, such as cigarette smoke. The mechanism of this synergistic interaction is unknown. It is worth noting that the SE has recently been found to act as a signal transduction ligand that facilitates differentiation of Th17 cells and osteoclasts in vitro and in vivo...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29665497/the-effects-of-resiquimod-in-an-ovalbumin-induced-allergic-rhinitis-model
#2
Shenhong Qu, Taijie Qin, Min Li, Shaojie Zhang, Linsong Ye, Jiazhang Wei, Hua Fan, Baiwen Chen
Growing evidence indicates that the Toll-like receptor7/8(TLR7/8) agonist resiquimod (R848) is a potential inhibitor of type-2 immunity. However, the mechanisms mediating its therapeutic effects are not fully understood. This study investigated the effects of R848 on OVA-induced allergic rhinitis(AR) mice and the expression of IL-25, IL-33, TSLP, T-cell immunoglobulin mucin1 (TIM1) and T-cell immunoglobulin mucin3 (TIM3). BALB/c mice were intranasally sensitized and challenged with ovalbumin (OVA), and R848 was intraperitoneally injected into AR mice...
April 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29665238/cp-25-alleviates-experimental-sj%C3%A3-gren-s-syndrome-features-in-nod-ltj-mice-and-modulates-t-lymphocyte-subsets
#3
Fang Gu, Shixia Xu, Pengying Zhang, Xiaoyun Chen, Yujing Wu, Chun Wang, Mei Gao, Min Si, Xinming Wang, Korner Heinrich, Huaxun Wu, Wei Wei
Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune illness of the moisture-producing glands such as salivary glands that is characterized by various immune abnormalities. The aetiology of pSS remains unclear and there is no curative agent. In this study, we investigated the putative therapeutic effects on a NOD/Ltj mouse model of Sjögren's syndrome-like disorders of an ester derivative of paeoniflorin, Paeoniflorin-6'O-benzene (termed CP-25). Our study showed that CP-25 alleviated effectively clinical manifestations in NOD/Ltj mice resulting for example in increased salivary flow and reduced histopathological scores...
April 17, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29664967/role-of-il-23-signaling-in-the-progression-of-premalignant-oral-lesions-to-cancer
#4
Blaine Caughron, Yi Yang, M Rita I Young
Mice bearing carcinogen-induced premalignant oral lesions were previously shown to have a pro-inflammatory phenotype, which is replaced with an immune inhibitory phenotype as lesions progress to cancer. Since Th17 cells are prominent at the premalignant lesion state and their levels are supported by IL-23, studies used mice that were IL-23 receptor deficient (IL-23R KO) to determine the requirement for IL-23 signaling in the immunological and clinical status of mice with premalignant oral lesions. The results showed a dependence on IL-23 signaling for the pro-inflammatory state of mice with oral lesions as levels of IL-2, IFN-γ, IL-6, IL-17 and TNF-α were elevated in wildtype mice with premalignant oral lesions, but not in IL-23R KO mice...
2018: PloS One
https://www.readbyqxmd.com/read/29663372/regulatory-t-and-t-helper-17-cells-their-roles-in-preeclampsia
#5
REVIEW
Arezoo Hosseini, Sanam Dolati, Vida Hashemi, Meghdad Abdollahpour-Alitappeh, Mehdi Yousefi
Regulatory T (Treg) cells have been identified as key immune regulators and are important to fetal survival within the maternal uterus. T helper 17 (Th17) cells have also emerged as a new subset of effector helper T cells and play significant roles in host defense against extracellular pathogens, autoimmune conditions, and inflammatory chronic diseases. Recent findings have provided strong support for the contribution of Th17 and Treg cells to successful pregnancy. Disorders of pregnancy such as preeclampsia (PE) and recurrent spontaneous abortion (RSA) are associated with low frequencies of Treg cells and high levels of Th17 cells...
April 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29662488/subretinal-injection-of-hy-peptides-induces-systemic-antigen-specific-inhibition-of-effector-cd4-and-cd8-t-cell-responses
#6
Julie Vendomèle, Safa Dehmani, Quentin Khebizi, Anne Galy, Sylvain Fisson
Purpose: Injection of an antigen into the anterior chamber of the eye induces a peripheral antigen-specific immune modulation mechanism, known as anterior chamber-associated immune deviation (ACAID). Delayed-type hypersensitivity experiments argue that the subretinal space (SR) of the eye displays properties similar to ACAID. However, no investigation was performed regarding the differential impact of a subretinal antigen injection on peripheral CD4+ versus CD8+ T cells, on the potential immune deviation regarding Th profiles, and on the antigen-specificity of the inhibition...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29660509/glycosylation-enhanced-biocompatibility-of-the-supramolecular-hydrogel-of-an-anti-inflammatory-drug-for-topical-suppression-of-inflammation
#7
Taotao Xiong, Xianglian Li, Yanfang Zhou, Qianqian Song, Renshu Zhang, Lei Lei, Xingyi Li
Intravitreal/periocular injection of triamcinolone acetonide (TA) suspension is a common uveitis treatment, but it displays a high risk for serious side effects (e.g., high intraocular pressure, retinal toxicity). We report here an intravitreally injectable thermosensitive glycosylated TA (TA-SA-Glu) hydrogel, formed by covalently conjugating glucosamine (Glu) with succinate TA (TA-SA), for treating uveitis. The TA-SA-Glu hydrogelator forms a supramolecular hydrogel spontaneously in aqueous solution with a minimal gelation concentration of 0...
April 13, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29659729/t-helper-17-1-cells-associate-with-multiple-sclerosis-disease-activity-perspectives-for-early-intervention
#8
Jamie van Langelaar, Roos M van der Vuurst de Vries, Malou Janssen, Annet F Wierenga-Wolf, Isis M Spilt, Theodora A Siepman, Wendy Dankers, Georges M G M Verjans, Helga E de Vries, Erik Lubberts, Rogier Q Hintzen, Marvin M van Luijn
Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients...
April 5, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29659554/demyelination-in-multiple-sclerosis-reprogramming-energy-metabolism-and-potential-ppar%C3%AE-agonist-treatment-approaches
#9
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Demyelination in multiple sclerosis (MS) cells is the site of several energy metabolic abnormalities driven by dysregulation between the opposed interplay of peroxisome proliferator-activated receptor γ (PPARγ) and WNT/β-catenin pathways. We focus our review on the opposing interactions observed in demyelinating processes in MS between the canonical WNT/β-catenin pathway and PPARγ and their reprogramming energy metabolism implications. Demyelination in MS is associated with chronic inflammation, which is itself associated with the release of cytokines by CD4⁺ Th17 cells, and downregulation of PPARγ expression leading to the upregulation of the WNT/β-catenin pathway...
April 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29659179/nk-cell-and-th17-responses-are-differentially-induced-in-murine-cytomegalovirus-infected-renal-allografts-and-vary-according-to-recipient-virus-dose-and-strain
#10
Mao Li, Srinivasa Boddeda, Bo Chen, Qiang Zeng, Trenton R Schoeb, Victoria M Velazquez, Masako Shimamura
Human cytomegalovirus (HCMV) donor positive (D+) serostatus with acute rejection is associated with renal allograft loss, but the impact of recipient positive (R+) serostatus is unclear. In an allogeneic renal transplant model, antiviral natural killer (NK) and CD8+ T cell memory responses in murine CMV (MCMV) D+/R+ transplants were compared to D-/R- and D+/R- transplants, with recipient infection varied by MCMV dose and strain. D+/R- transplants had high primary antiviral cytolytic (interferon-γ+) and cytotoxic (granzyme B+) NK responses, whereas NK memory responses were lower in D+/R+ recipients receiving a high primary MCMV dose...
April 16, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29657243/distinct-pattern-of-th17-treg-cells-in-pregnant-women-with-a-history-of-unexplained-recurrent-spontaneous-abortion
#11
Jinfeng Qian, Na Zhang, Jing Lin, Caiyan Wang, Xinyao Pan, Lanting Chen, Dajin Li, Ling Wang
The aim of the current study was to determine the pattern of immune cells and related functional molecules in peripheral blood and at the maternal-fetal interface in women with unexplained recurrent spontaneous abortion (URSA). In part I, 155 women were included and divided into four groups: non-pregnant controls with no history of URSA (NPCs), pregnant controls with no history of URSA (PCs), non-pregnant women with a history of URSA (NPUs), and pregnant women with a history of URSA (PUs). Venous blood samples were collected and analyzed...
April 15, 2018: Bioscience Trends
https://www.readbyqxmd.com/read/29656243/different-permeabilization-patterns-of-splenocytes-and-thymocytes-to-combination-of-pulsed-electric-and-magnetic-field-treatments
#12
Vitalij Novickij, Auksė Zinkevičienė, Justinas Valiulis, Jurgita Švedienė, Algimantas Paškevičius, Eglė Lastauskienė, Svetlana Markovskaja, Jurij Novickij, Irutė Girkontaitė
Genetic manipulation of T cells is frequently inefficient, however, when combined with physical methods (i.e. electroporation) a promising alliance with immunotherapy can be formed. This study presents new data on permeabilization of murine thymocytes and splenocytes as a T cell model using pulsed electric (PEF) and electromagnetic field (EMF). The 300ns, 500ns, 2μs and 100μs pulse bursts in a broad range of PEF 0-8kV/cm were applied separately and in combination with 3.3T, 0.2kV/cm EMF pulses. The permeabilization efficiency was evaluated using fluorescent dye (YO-PRO-1) and flow cytometry...
April 10, 2018: Bioelectrochemistry
https://www.readbyqxmd.com/read/29656211/esculetin-from-fraxinus-rhynchophylla-attenuates-atopic-skin-inflammation-by-inhibiting-the-expression-of-inflammatory-cytokines
#13
Na-Hee Jeong, Eun-Ju Yang, Meiling Jin, Jong Yeong Lee, Young-Ae Choi, Pil-Hoon Park, Sang-Rae Lee, Sun-Uk Kim, Tae-Yong Shin, Taeg Kyu Kwon, Yong Hyun Jang, Kyung-Sik Song, Sang-Hyun Kim
Atopic dermatitis (AD) is a common chronic inflammatory skin disorder afflicting from infancy to adults with itching, scratching, and lichenification. We aimed to investigate the effects of esculetin from Fraxinus rhynchophylla on atopic skin inflammation. For induction of atopic skin inflammation, we exposed the ears of female BALB/c mice to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB) for 4 weeks. Oral administration of esculetin reduced the symptoms of DFE/DNCB-induced atopic skin inflammation, which were evaluated based on ear swelling and number of scratch bouts...
April 12, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29656117/baicalin-modulates-the-treg-teff-balance-to-alleviate-uveitis-by-activating-the-aryl-hydrocarbon-receptor
#14
Wenjie Zhu, Xiaoqing Chen, Jianfeng Yu, Yichen Xiao, Yingqi Li, Shangtao Wan, Wenru Su, Dan Liang
Autoimmune uveitis is a sight-threatening ocular inflammatory disorder. Immunological inflammation is regarded as the key to pathogenesis in autoimmune uveitis. Baicalin, the major bioactive component of Scutellaria baicalensis, possesses immunomodulatory properties. However, the role of baicalin in uveitis and its underlying mechanisms remain unclear. In the current study, we found that baicalin treatment obviously inhibited the intraocular inflammatory process in mice with experimental autoimmune uveitis, along with clear declines in infiltrated inflammatory cells and inflammatory cytokine transcription in the retina and draining lymph nodes...
April 12, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29655629/intramuscular-vaccination-of-guinea-pigs-with-the-live-attenuated-human-herpes-simplex-vaccine-vc2-stimulates-a-transcriptional-profile-of-vaginal-th17-and-regulatory-tr1-responses
#15
Brent A Stanfield, Paul J F Rider, John Caskey, Fabio Del Piero, Konstantin G Kousoulas
Herpes simplex virus is a common causative agent of oral and genital diseases. Novel vaccines and therapeutics are needed to combat herpes infections especially after the failure of subunit vaccines in human clinical trials. We have shown that the live-attenuated HSV-1 VC2 vaccine strain is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. The guinea pig represents the best small animal model of genital HSV-2 disease...
April 11, 2018: Vaccine
https://www.readbyqxmd.com/read/29651155/epigenetic-activation-during-t-helper-17-cell-differentiation-is-mediated-by-tripartite-motif-containing-28
#16
Yu Jiang, Ying Liu, Huiping Lu, Shao-Cong Sun, Wei Jin, Xiaohu Wang, Chen Dong
Epigenetic regulation is important for T-cell fate decision. Although STAT3 is known to initiate Th17 differentiation program, the downstream mechanism is unclear. Here we show that Tripartite motif containing 28 (Trim28) expression in Th17 cells is required for Th17-mediated cytokine production and experimental autoimmune diseases. Genome-wide occupancy analysis reveals that TRIM28-bound regions overlap with almost all Th17-specific super-enhancers (SE), and that those SEs are impaired by the deficiency of STAT3 or TRIM28, but not of RORγt...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29644622/microbial-metabolites-short-chain-fatty-acids-restrain-tissue-bacterial-load-chronic-inflammation-and-associated-cancer-in-the-colon-of-mice
#17
Myunghoo Kim, Leon Friesen, Jeongho Park, Hyungjin M Kim, Chang H Kim
The intestinal immune system is regulated by microbes and their metabolites. The roles of gut microbial metabolites in regulating intestinal inflammation and tumorigenesis are incompletely understood. We systematically studied the roles of short-chain fatty acids (SCFAs) and their receptors (GPR43 or GPR41) in regulating tissue bacterial load, acute versus chronic inflammatory responses, and intestinal cancer development. SCFA receptor-, particularly GPR43-, deficient mice were defective in mounting appropriate acute immune responses to promote barrier immunity, and developed uncontrolled chronic inflammatory responses following epithelial damage...
April 12, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29629900/recipient-mucosal-associated-invariant-t-cells-control-gvhd-within-the-colon
#18
Antiopi Varelias, Mark D Bunting, Kate L Ormerod, Motoko Koyama, Stuart D Olver, Jasmin Straube, Rachel D Kuns, Renee J Robb, Andrea S Henden, Leanne Cooper, Nancy Lachner, Kate H Gartlan, Olivier Lantz, Lars Kjer-Nielsen, Jeffrey Yw Mak, David P Fairlie, Andrew D Clouston, James McCluskey, Jamie Rossjohn, Steven W Lane, Philip Hugenholtz, Geoffrey R Hill
Mucosal-associated invariant T (MAIT) cells are a unique innate-like T cell subset that responds to a wide array of bacteria and yeast through recognition of riboflavin metabolites presented by the MHC class I-like molecule MR1. Here, we demonstrate using MR1 tetramers that recipient MAIT cells are present in small but definable numbers in graft-versus-host disease (GVHD) target organs and protect from acute GVHD in the colon following bone marrow transplantation (BMT). Consistent with their preferential juxtaposition to microbial signals in the colon, recipient MAIT cells generate large amounts of IL-17A, promote gastrointestinal tract integrity, and limit the donor alloantigen presentation that in turn drives donor Th1 and Th17 expansion specifically in the colon after BMT...
April 9, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29627423/a-jagged1-notch4-molecular-switch-mediates-airway-inflammation-by-ultrafine-particles
#19
Mingcan Xia, Hani Harb, Arian Saffari, Constantinos Sioutas, Talal A Chatila
BACKGROUND: Exposure to traffic-related particulate matter (PM) promotes asthma and allergic diseases. However, the precise cellular and molecular mechanisms by which PM exposure acts to mediate these effects remain unclear. OBJECTIVE: We sought to elucidate the cellular targets and signaling pathways critical for the augmentation of allergic airway inflammation induced by ambient ultra fine particles (UFP). METHODS: We employed in vitro cell culture assays using lung-derived antigen presenting cells and allergen-specific T cells, and in vivo mouse models of allergic airway inflammation that employed myeloid lineage-specific gene deletions, cellular reconstitution approaches and antibody inhibition studies...
April 5, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29627063/high-fiber-dietary-and-sodium-butyrate-attenuate-experimental-autoimmune-hepatitis-through-regulation-of-immune-regulatory-cells-and-intestinal-barrier
#20
En-De Hu, Da-Zhi Chen, Jin-Lu Wu, Feng-Bin Lu, Lu Chen, Ming-Hua Zheng, Hui Li, Yu Huang, Ji Li, Xiao-Ya Jin, Yue-Wen Gong, Zhuo Lin, Xiao-Dong Wang, Lan-Man Xu, Yong-Ping Chen
Autoimmune hepatitis (AIH) is chronic autoimmune liver disease accompanied with the imbalance of Treg/Th17 and increased intestinal permeability. We investigated the effects of a high fiber diet and sodium butyrate on the Treg/Th17 and intestinal barrier function in an experimental autoimmune hepatitis. Intraperitoneal injection of hepatic antigen (S100) was used to induce experimental autoimmune hepatitis mice model and mice were divided into normal control, S100 model control, S100 plus high fiber diet and S100 plus sodium butyrate...
March 22, 2018: Cellular Immunology
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