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Treg autoimmunity

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https://www.readbyqxmd.com/read/29331869/dietary-naringenin-supplementation-attenuates-experimental-autoimmune-encephalomyelitis-by-modulating-autoimmune-inflammatory-responses-in-mice
#1
Junpeng Wang, Ying Qi, Xinli Niu, Hua Tang, Simin Nikbin Meydani, Dayong Wu
Autoimmune disease is highly prevalent in humans. Since conventional therapies have limited efficacy and often come with significant side effects, nutrition may provide an alternative and complementary approach to improving autoimmune disorders. Naringenin, a flavonoid found in citrus fruits, has been shown to have anti-inflammatory and antioxidant properties. Using the experimental autoimmune encephalomyelitis (EAE), a rodent model of human multiple sclerosis, we determined the effect of dietary naringenin (0...
December 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29326066/novel-everolimus-loaded-nanocarriers-for-topical-treatment-of-murine-experimental-autoimmune-uveoretinitis-eau
#2
Maren Kasper, Doris Gabriel, Michael Möller, Dirk Bauer, Lena Wildschütz, Herve Courthion, Michael R R Böhm, Martin Busch, Karin Loser, Solon Thanos, Robert Gurny, Arnd Heiligenhaus
In the present study, therapeutic effect of topically applied everolimus (EV)-loaded methoxy-poly(ethylene-glycol)-hexyl substituted poly (lactic acid) (mPEGhexPLA) nanocarriers on experimental autoimmune uveitis (EAU) were investigated. EAU was induced in B10.RIII mice via immunization with human interphotoreceptor retinoid-binding protein peptide 161-180 (hIRBPp161-180) in complete Freund's adjuvant. Everolimus-loaded mPEGhexPLA (EV/mPEGhexPLA) nanocarriers were prepared by using a solvent evaporation method...
January 8, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29323337/regulatory-t-cells-as-a-new-therapeutic-target-for-atherosclerosis
#3
REVIEW
Han-Xiao Ou, Bing-Bing Guo, Qi Liu, Yu-Kun Li, Zhen Yang, Wen-Jie Feng, Zhong-Cheng Mo
Atherosclerosis is an autoimmune disease caused by self- and non-self-antigens contributing to excessive activation of T and B cell immune responses. These responses further aggravate vascular inflammation and promote progression of atherosclerosis and vulnerability to plaques via releasing pro-inflammatory cytokines. Regulatory T cells (Tregs) as the major immunoregulatory cells, in particular, induce and maintain immune homeostasis and tolerance by suppressing the immune responses of various cells such as T and B cells, natural killer (NK) cells, monocytes, and dendritic cells (DCs), as well as by secreting inhibitory cytokines interleukin (IL)-10, IL-35 and transcription growth factor β (TGF-β) in both physiological and pathological states...
January 11, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29321652/innate-ifn-%C3%AE-ameliorates-experimental-autoimmune-encephalomyelitis-and-promotes-myeloid-expansion-and-pdl-1-expression
#4
Madeleine P J White, Gill Webster, Faith Leonard, Anne Camille La Flamme
The innate immune system plays a central role in the immune-mediated pathology of multiple sclerosis, and is a therapeutic target for progressive disease. Recently, it has been demonstrated that MIS416, a novel immunomodulatory microparticle that activates NOD-2 and TLR-9-signaling, has disease-modifying activity in multiple sclerosis models. This activity is dependent on innate IFN-γ; however, the precise immune regulatory mechanisms amplified by MIS416 have not previously been determined. Using the experimental autoimmune encephalomyelitis model, MIS416 treatment was associated with IFN-γ-dependant expansion of Treg number and increased suppressive function; however, these cells did not account for disease reduction...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311129/regulatory-t-cells-from-discovery-to-autoimmunity
#5
Alexandra Kitz, Emily Singer, David Hafler
Multiple sclerosis (MS) is a genetically mediated autoimmune disease of the central nervous system. Allelic variants lead to lower thresholds of T-cell activation resulting in activation of autoreactive T cells. Environmental factors, including, among others, diet, vitamin D, and smoking, in combination with genetic predispositions, play a substantial role in disease development and activation of autoreactive T cells. FoxP3+ regulatory T cells (Tregs) have emerged as central in the control of autoreactive T cells...
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29310925/th17-lineage-cells-in-pulmonary-sarcoidosis-and-l%C3%A3-fgren-s-syndrome-friend-or-foe
#6
REVIEW
Jelle R Miedema, Ylva Kaiser, Caroline E Broos, Marlies S Wijsenbeek, Johan Grunewald, Mirjam Kool
Sarcoidosis, a multisystem granulomatous disorder, has historically been classified as Th1-driven disease. However, increasing data demonstrate a key role of Th17-cell plasticity in granuloma formation and maintenance. In Löfgren's syndrome (LS), an acute and distinct phenotype of sarcoidosis with a favorable outcome, differences in Th17-lineage cell subsets, cytokine expression and T-cell suppressive mechanisms may account for differences in clinical presentation as well as prognosis compared to non-LS sarcoidosis...
January 5, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29305966/study-of-an-extended-family-with-ctla-4-deficiency-suggests-a-cd28-ctla-4-independent-mechanism-responsible-for-differences-in-disease-manifestations-and-severity
#7
Tie Zheng Hou, Peter Olbrich, Jose Manuel Lucena Soto, Berta Sanchez, Paula Sanchez Moreno, Stephan Borte, Hans J Stauss, Siobhan O Burns, Lucy S K Walker, Qiang Pan-Hammarström, Lennart Hammarström, David M Sansom, Olaf Neth
The CTLA-4 checkpoint regulates the activation of T cells. Individuals with heterozygous mutations in CTLA-4 have a complex phenotype typically characterized by antibody deficiency alongside variable autoimmunity. Despite severe disease in some individuals, others remain largely unaffected with reasons for this variation unknown. We studied a large family carrying a single point mutation in CTLA-4 leading to an amino acid change R75W and compared both unaffected with affected individuals. We measured a variety of features pertaining to T cell and CTLA-4 biology and observed that at the cellular level there was complete penetrance of CTLA-4 mutations...
January 3, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29305419/the-molecular-basis-of-immune-regulation-in-autoimmunity
#8
REVIEW
Shu-Han Yang, Cai-Yue Gao, Liang Li, Christopher Chang, Patrick S C Leung, M Eric Gershwin, Zhe-Xiong Lian
Autoimmune diseases can be triggered and modulated by various molecular and cellular characteristics. The mechanisms of autoimmunity and the pathogenesis of autoimmune diseases have been investigated for several decades. It is well accepted that autoimmunity is caused by dysregulated/dysfunctional immune susceptible genes and environmental factors. There are multiple physiological mechanisms that regulate and control self-reactivity, but which can also lead to tolerance breakdown when in defect. The majority of autoreactive T or B cells are eliminated during the development of central tolerance by negative selection...
January 16, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29298866/a-mirna181a-nfat5-axis-links-impaired-t-cell-tolerance-induction-with-autoimmune-type-1-diabetes
#9
Isabelle Serr, Martin G Scherm, Adam M Zahm, Jonathan Schug, Victoria K Flynn, Markus Hippich, Stefanie Kälin, Maike Becker, Peter Achenbach, Alexei Nikolaev, Katharina Gerlach, Nicole Liebsch, Brigitta Loretz, Claus-Michael Lehr, Benedikt Kirchner, Melanie Spornraft, Bettina Haase, James Segars, Christoph Küper, Ralf Palmisano, Ari Waisman, Richard A Willis, Wan-Uk Kim, Benno Weigmann, Klaus H Kaestner, Anette-Gabriele Ziegler, Carolin Daniel
Molecular checkpoints that trigger the onset of islet autoimmunity or progression to human type 1 diabetes (T1D) are incompletely understood. Using T cells from children at an early stage of islet autoimmunity without clinical T1D, we find that a microRNA181a (miRNA181a)-mediated increase in signal strength of stimulation and costimulation links nuclear factor of activated T cells 5 (NFAT5) with impaired tolerance induction and autoimmune activation. We show that enhancing miRNA181a activity increases NFAT5 expression while inhibiting FOXP3+ regulatory T cell (Treg) induction in vitro...
January 3, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29298831/role-of-the-nf-%C3%AE%C2%BAb-family-member-relb-in-regulation-of-foxp3-regulatory-t-cells-in-vivo
#10
Junhui Li, Shuqiu Chen, Wenhao Chen, Qifa Ye, Yaling Dou, Yue Xiao, Lei Zhang, Laurie J Minze, Xian C Li, Xiang Xiao
The NF-κB family member RelB is an important transcription factor that is capable of regulating diverse immune and inflammatory responses. However, its role in the regulation of Foxp3+ regulatory T cells (Tregs) in vivo is poorly defined. In this study, we demonstrated that germline deletion of Relb resulted in systemic autoimmunity, which is associated with significant accumulation of Foxp3+ Tregs in lymphoid and nonlymphoid organs. Foxp3+ Tregs from RelB-deficient mice were functional and capable of suppressing T effector cells in vitro and in vivo, but Foxp3- T effector cells from RelB-deficient mice showed features of hyperactivation and spontaneously produced high levels of IL-2...
January 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29297233/deficiency-of-autoimmune-regulator-impairs-the-immune-tolerance-effect-of-bone-marrow-derived-dendritic-cells-in-mice
#11
Feifei Huo, Dongbei Li, Bo Zhao, Yadong Luo, Bingjie Zhao, Xueyang Zou, Yi Li, Wei Yang
As a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that affect the differentiation of T cells toward distinct subpopulations and participate in the immune response and tolerance, thereby playing an important role in maintaining homeostasis...
January 3, 2018: Autoimmunity
https://www.readbyqxmd.com/read/29295981/circulating-exosomes-suppress-the-induction-of-regulatory-t-cells-via-let-7i-in-multiple-sclerosis
#12
Kimitoshi Kimura, Hirohiko Hohjoh, Masashi Fukuoka, Wakiro Sato, Shinji Oki, Chiharu Tomi, Hiromi Yamaguchi, Takayuki Kondo, Ryosuke Takahashi, Takashi Yamamura
Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system. Foxp3+ regulatory T (Treg) cells are reduced in frequency and dysfunctional in patients with MS, but the underlying mechanisms of this deficiency are unclear. Here, we show that induction of human IFN-γ-IL-17A-Foxp3+CD4+ T cells is inhibited in the presence of circulating exosomes from patients with MS. The exosomal miRNA profile of patients with MS differs from that of healthy controls, and let-7i, which is markedly increased in patients with MS, suppresses induction of Treg cells by targeting insulin like growth factor 1 receptor (IGF1R) and transforming growth factor beta receptor 1 (TGFBR1)...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29288692/intraepithelial-cd8-lymphocytes-as-a-predictive-diagnostic-biomarker-for-the-remission-of-oral-lichen-planus
#13
Ai Enomoto, Eiichi Sato, Takashi Yasuda, Tatsuya Isomura, Toshitaka Nagao, Daichi Chikazu
Oral lichen planus (OLP) is an autoimmune inflammatory disease of the oral mucosa whose etiology remains unknown. Moreover, the possibility of OLP being a premalignant change is under debate. Various types of immune cells infiltrate the OLP lesion and affect its clinicopathological features. However, the diversity of infiltrating immune cells has not been fully clarified in relation to OLP diagnosis. In this study, we quantitatively examined CD8 (+) lymphocyte infiltration by immunohistochemistry, which is the principal effector of cytotoxic immune reaction in 123 cases of OLP specimens...
December 27, 2017: Human Pathology
https://www.readbyqxmd.com/read/29285209/combination-of-il-2-rapamycin-dna-methyltransferase-and-histone-deacetylase-inhibitors-for-the-expansion-of-human-regulatory-t-cells
#14
Makoto Miyara, Driss Chader, Aude Burlion, Jérémie Goldstein, Delphine Sterlin, Françoise Norol, Hélène Trebeden-Nègre, Laetitia Claër, Shimon Sakaguchi, Gilles Marodon, Zahir Amoura, Guy Gorochov
FOXP3+ regulatory T cell (Treg) based cellular therapies represent promising therapeutic options in autoimmunity, allergy, transplantation and prevention of Graft Versus Host (GVH) Disease. Among human FOXP3-expressing CD4+T cells, only the CD45RA+ naïve Treg (nTreg) subset is suitable for in vitro expansion. However, FoxP3 expression decays in cells using currently described culture protocols. Rapamycin alone was not able to prevent FOXP3 loss in nTregs cells, as only a half of them maintained FOXP3 expression after 14 days of culture...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29283462/role-of-t-helper-17-cells-and-t-regulatory-cells-in-alopecia-areata-comparison-of-lesion-and-serum-cytokine-between-controls-and-patients
#15
Seung-Hee Loh, Hae-Na Moon, Bark-Lynn Lew, Woo-Young Sim
BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease with T-cell-mediated attack of hair follicle autoantigens. As T-helper 17 (Th17) cells and T regulatory (Treg) cells are crucially involved in the pathogenesis, the role of Th17 and Treg cytokines has not been studied yet. OBJECTIVE: To determine whether AA is associated with alterations in lesional and serum Th17 and Treg cytokines, and studied whether they were associated with clinical type...
December 28, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29282307/cutting-edge-low-affinity-tcrs-support-regulatory-t-cell-function-in-autoimmunity
#16
Maran L Sprouse, Ivan Shevchenko, Marissa A Scavuzzo, Faith Joseph, Thomas Lee, Samuel Blum, Malgorzata Borowiak, Matthew L Bettini, Maria Bettini
Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3, suggesting distinct functional profiles...
December 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29274729/gemcitabine-directly-inhibits-effector-cd4-t-cell-activation-and-prevents-experimental-autoimmune-encephalomyelitis
#17
Justin D Glenn, Patrick Xue, Katharine A Whartenby
Pro-inflammatory T cells are critical to the pathogenesis of multiple sclerosis (MS). We investigated the potential for the anti-proliferative, pro-apoptotic drug gemcitabine to affect development of MS-relevant effector TH1, TH17, and Treg cells. Gemcitabine directly suppressed proliferation, activation, and induced apoptosis of all effector subsets in subtype and dose-dependent fashion. This drug also prevented development of disease in the MS model experimental autoimmune encephalomyelitis (EAE) and significantly reduced the abundance of TH1 and TH17 cells...
December 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29259988/increased-circulating-th17-but-decreased-cd4-foxp3-treg-and-cd19-cd1dhicd5-breg-subsets-in-new-onset-graves-disease
#18
Jing Qin, Jin Zhou, Chenling Fan, Na Zhao, Yongping Liu, Shuo Wang, Xuejiao Cui, Mingshi Huang, Haixia Guan, Yushu Li, Zhongyan Shan, Weiping Teng
Th17 and regulatory lymphocyte subsets such as Tregs and Bregs have been reported to play important roles in autoimmune diseases. The aim of this work was to perform quantitative studies of circulating Th17, Tregs, and Bregs in patients with new-onset Graves' disease (GD). Twenty GD patients and 20 healthy controls were involved in this study. Blood samples were taken for flow cytometry detection of CD4+IL-17+ Th17, CD4+Foxp3+ Tregs, and CD19+CD1dhiCD5+ Bregs and meanwhile, for real-time PCR measurement of gene expressions of RORγt, IL-17 and IL-10...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29259102/altered-homeostasis-and-development-of-regulatory-t-cell-subsets-represent-an-il-2r-dependent-risk-for-diabetes-in-nod-mice
#19
Connor J Dwyer, Allison L Bayer, Carmen Fotino, Liping Yu, Cecilia Cabello-Kindelan, Natasha C Ward, Kevin H Toomer, Zhibin Chen, Thomas R Malek
The cytokine interleukin-2 (IL-2) is critical for the functions of regulatory T cells (Tregs). The contribution of polymorphisms in the gene encoding the IL-2 receptor α subunit (IL2RA), which are associated with type 1 diabetes, is difficult to determine because autoimmunity depends on variations in multiple genes, where the contribution of any one gene product is small. We investigated the mechanisms whereby a modest reduction in IL-2R signaling selectively in T lymphocytes influenced the development of diabetes in the NOD mouse model...
December 19, 2017: Science Signaling
https://www.readbyqxmd.com/read/29246441/roquin-suppresses-the-pi3k-mtor-signaling-pathway-to-inhibit-t-helper-cell-differentiation-and-conversion-of-treg-to-tfr-cells
#20
Katharina Essig, Desheng Hu, Joao C Guimaraes, Dominik Alterauge, Stephanie Edelmann, Timsse Raj, Jan Kranich, Gesine Behrens, Alexander Heiseke, Stefan Floess, Juliane Klein, Andreas Maiser, Susan Marschall, Martin Hrabĕ de Angelis, Heinrich Leonhardt, Cornelis F Calkhoven, Elfriede Noessner, Thomas Brocker, Jochen Huehn, Anne B Krug, Mihaela Zavolan, Dirk Baumjohann, Vigo Heissmeyer
Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17∼92 binding to an overlapping cis-element in the Pten 3' UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch...
December 12, 2017: Immunity
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