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Treg autoimmunity

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https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#1
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28638223/clinical-significance-of-changes-in-the-th17-treg-ratio-in-autoimmune-liver-disease
#2
Ting-Ting Feng, Ting Zou, Xin Wang, Wei-Feng Zhao, Ai-Lan Qin
AIM: To investigate the levels, ratios, and clinical significance of T helper 17 (Th17) cells and regulatory T (Treg) cells in the peripheral blood of patients with autoimmune liver disease (AILD). METHODS: Forty-two AILD patients were included in the experimental group (group E), and 11 healthy subjects were recruited as the control group (group C). Flow cytometry was performed to determine the percentages of Th17 and Treg cells in peripheral blood lymphocytes...
June 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28634589/hla-class-ia-and-ib-polyreactive-anti-hla-e-igg2a-monoclonal-antibodies-tfl-006-and-tfl-007-suppress-anti-hla-igg-production-by-cd19-b-cells-and-proliferation-of-cd4-t-cells-while-upregulating-tregs
#3
REVIEW
Mepur H Ravindranath
The anti-HLA-E IgG2a mAbs, TFL-006 and TFL-007, reacted with all HLA-I antigens, similar to the therapeutic preparations of IVIg. Indeed, IVIg lost its HLA reactivity, when its HLA-E reactivity was adsorbed out. US-FDA approved IVIg to reduce antibodies in autoimmune diseases. But the mechanism underlying IVIg-mediated antibody reduction could not be ascertained due to the presence of other polyclonal antibodies. In spite of it, the cost prohibitive high or low IVIg is administered to patients waiting for donor organ and for allograft recipients for lowering antiallograft antibodies...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28631092/rituximab-treatment-in-pemphigus-vulgaris-effect-on-circulating-tregs
#4
Bakr El-Zawahry, Dalia Bassiouny, Rehab Hegazy, Heba Gawdat, Suzan Shalaby, Mervat Khorshied, Marwah Adly Saleh
Rituximab (RTX) has been used successfully to treat refractory pemphigus. We aimed to assess the response of pemphigus vulgaris (PV) cases to RTX therapy and its effect on CD4(+)CD25(+) (T regulatory) cells level. Sixteen PV patients were included in this study, each received one cycle of two RTX infusions (1000 mg on days 1 and 15). Five PV patients served as controls. All cases were on prednisolone ± adjuvant therapy. Pemphigus disease area index (PDAI), autoimmune bullous skin intensity score (ABSIS), anti-desmoglein antibodies, CD4, CD8, CD20 and CD4(+)CD25(+) levels were assessed at baseline, 3, 6 and 12 months after therapy...
June 19, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28630387/assessment-of-t-helper-17-associated-cytokines-in-third-trimester-of-pregnancy
#5
Tahereh Poordast, Fateme Sadat Najib, Rasoul Baharlou, Atena Bijani, Shaghayegh Moradi Alamdarloo, Alieh Poordast
BACKGROUND: Preeclampsia is a common pregnancy-specific disorder associated with significant maternal and fetal morbidity and mortality worldwide. It has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Treg) and T-helper 17 cells (Th17), is involved in the pathophysiology of preeclampsia. OBJECTIVES: To determine the serum levels of IL-17, IL-21, IL-23 and TGF-β in patients with preeclampsia. METHODS: Blood samples were collected from 30 preeclampsia patients, 30 normotensive pregnant women and 30 healthy individuals with no history of malignancies or autoimmune disorders based on simple sampling...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28621313/lkb1-maintains-treg-cell-lineage-identity
#6
Di Wu, Yuechen Luo, Wei Guo, Qing Niu, Ting Xue, Fei Yang, Xiaolei Sun, Song Chen, Yuanyuan Liu, Jingru Liu, Zhina Sun, Chunxiao Zhao, Huifang Huang, Fang Liao, Zhongchao Han, Dongming Zhou, Yongguang Yang, Guogang Xu, Tao Cheng, Xiaoming Feng
Regulatory T (Treg) cells are a distinct T-cell lineage characterized by sustained Foxp3 expression and potent suppressor function, but the upstream dominant factors that preserve Treg lineage-specific features are mostly unknown. Here, we show that Lkb1 maintains Treg cell lineage identity by stabilizing Foxp3 expression and enforcing suppressor function. Upon T-cell receptor (TCR) stimulation Lkb1 protein expression is upregulated in Treg cells but not in conventional T cells. Mice with Treg cell-specific deletion of Lkb1 develop a fatal early-onset autoimmune disease, with no Foxp3 expression in most Treg cells...
June 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28620098/cytokine-signaling-in-the-development-and-homeostasis-of-regulatory-t-cells
#7
Kevin H Toomer, Thomas R Malek
Cytokine signaling is indispensable for regulatory T-cell (Treg) development in the thymus, and also influences the homeostasis, phenotypic diversity, and function of Tregs in the periphery. Because Tregs are required for establishment and maintenance of immunological self-tolerance, investigating the role of cytokines in Treg biology carries therapeutic potential in the context of autoimmune disease. This review discusses the potent and diverse influences of interleukin (IL)-2 signaling on the Treg compartment, an area of knowledge that has led to the use of low-dose IL-2 as a therapy to reregulate autoaggressive immune responses...
June 15, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28618983/regulatory-t-cells-show-dynamic-behavior-during-late-pregnancy-delivery-and-the-postpartum-period
#8
Jorge Lima, Catarina Martins, Glória Nunes, Maria-José Sousa, Jorge C Branco, Luís-Miguel Borrego
Regulatory T cells (Tregs) are critical immunomodulators during early pregnancy by preventing maternal T-cell activation against fetal cells. However, how populations of maternal Tregs vary during and after pregnancy in humans is still unclear. Therefore, we investigated Treg subsets in the peripheral blood of pregnant women from late pregnancy through the postpartum period. To accomplish this, the following circulating Treg subsets were analyzed in 43 healthy pregnant women and 35 nonpregnant women by flow cytometry during the third trimester, on the day of delivery, and postpartum: CD4(Dim)CD25(Hi), CD4(+)CD25(Hi)Foxp3(+), and CD4(+)CD25(Hi)CD127(-/dim)...
July 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28617989/1-25-dihydroxyvitamin-d3-induced-dendritic-cells-suppress-experimental-autoimmune-encephalomyelitis-by-increasing-proportions-of-the-regulatory-lymphocytes-and-reducing-th1-th17-cells
#9
Zhongxiang Xie, Jingtao Chen, Chao Zheng, Jing Wu, Yun Cheng, Shan Zhu, Chenhong Lin, Qingqing Cao, Jie Zhu, Tao Jin
Dendritic cells (DCs), a bridge of innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in the autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) and adoptive transferred the tolerogenic DCs (VD3-DCs) into EAE mice...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28614408/schistosoma-japonicum-infection-downregulates-house-dust-mite-induced-allergic-airway-inflammation-in-mice
#10
Sugan Qiu, Xiaolin Fan, Yingying Yang, Panpan Dong, Wei Zhou, Yongliang Xu, Yonghua Zhou, Fukun Guo, Yi Zheng, Jun-Qi Yang
The "hygiene hypothesis" is a theory try to explain the dramatic increases in the prevalence of autoimmune and allergic diseases over the past two to three decades in developed countries. According to this theory, reduced exposure to parasites and microorganisms in childhood is the main cause for the increased incidences of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. In this study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma...
2017: PloS One
https://www.readbyqxmd.com/read/28611770/relevance-of-cd6-mediated-interactions-in-the-regulation-of-peripheral-t-cell-responses-and-tolerance
#11
Marta Consuegra-Fernández, Mario Martínez-Florensa, Fernando Aranda, José de Salort, Noelia Armiger-Borràs, Teresa Lozano, Noelia Casares, Juan José Lasarte, Pablo Engel, Francisco Lozano
The CD6 lymphocyte receptor has been involved in the pathophysiology of different autoimmune disorders and is now considered a feasible target for their treatment. In vitro data show the relevance of CD6 in the stabilization of adhesive contacts between T-cell and antigen-presenting cells, and the modulation of T-cell receptor signals. However, the in vivo consequences of such a function are yet undisclosed due to the lack of suitable genetically modified animal models. Here, the in vitro and in vivo challenge of CD6-deficient (CD6(-/-)) cells with allogeneic cells was used as an approach to explore the role of CD6 in immune responses under relative physiological stimulatory conditions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611475/murine-lrba-deficiency-causes-ctla-4-deficiency-in-tregs-without-progression-to-immune-dysregulation
#12
Deborah Burnett, Ian Parish, Etienne Masle-Farquhar, Robert Brink, Christopher Goodnow
Inherited mutations in Lipopolysaccharide Responsive Beige-like Anchor (LRBA) cause a recessive human immune dysregulation syndrome with memory B cell and antibody deficiency (common variable immunodeficiency, CVID), inflammatory bowel disease, enlarged spleen and lymph nodes, accumulation of activated T cells, and multiple autoimmune diseases. To understand the pathogenesis of the syndrome, C57BL/6 mice carrying a homozygous truncating mutation in Lrba were produced using CRISPR/Cas9-mediated gene targeting...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#13
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants and therefore liver transplantation offers an attractive setting in which to study tolerising therapies...
June 13, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28607488/stability-and-function-of-regulatory-t-cells-expressing-the-transcription-factor-t-bet
#14
Andrew G Levine, Alejandra Medoza, Saskia Hemmers, Bruno Moltedo, Rachel E Niec, Michail Schizas, Beatrice E Hoyos, Ekaterina V Putintseva, Ashutosh Chaudhry, Stanislav Dikiy, Sho Fujisawa, Dmitriy M Chudakov, Piper M Treuting, Alexander Y Rudensky
Adaptive immune responses are tailored to different types of pathogens through differentiation of naive CD4 T cells into functionally distinct subsets of effector T cells (T helper 1 (TH1), TH2, and TH17) defined by expression of the key transcription factors T-bet, GATA3, and RORγt, respectively. Regulatory T (Treg) cells comprise a distinct anti-inflammatory lineage specified by the X-linked transcription factor Foxp3 (refs 2, 3). Paradoxically, some activated Treg cells express the aforementioned effector CD4 T cell transcription factors, which have been suggested to provide Treg cells with enhanced suppressive capacity...
June 15, 2017: Nature
https://www.readbyqxmd.com/read/28604806/prostaglandin-e2-inhibits-tr1-cell-differentiation-through-suppression-of-c-maf
#15
Kirsten Mary Hooper, Weimin Kong, Doina Ganea
Prostaglandin E2 (PGE2), a major lipid mediator abundant at inflammatory sites, acts as a proinflammatory agent in models of inflammatory/autoimmune diseases by promoting CD4 Th1/Th17 differentiation. Regulatory T cells, including the IL-10 producing Tr1 cells counterbalance the proinflammatory activity of effector Th1/Th17 cells. Tr1 cell differentiation and function are induced by IL-27, and depend primarily on sustained expression of c-Maf in addition to AhR and Blimp-1. In agreement with the in vivo proinflammatory role of PGE2, here we report for the first time that PGE2 inhibits IL-27-induced differentiation and IL-10 production of murine CD4+CD49b+LAG-3+Foxp3- Tr1 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28603524/regulatory-t-cell-and-forkhead-box-protein-3-as-modulators-of-immune-homeostasis
#16
REVIEW
Leonn Mendes Soares Pereira, Samara Tatielle Monteiro Gomes, Ricardo Ishak, Antonio Carlos Rosário Vallinoto
The transcription factor forkhead box protein 3 (FOXP3) is an essential molecular marker of regulatory T cell (Treg) development in different microenvironments. Tregs are cells specialized in the suppression of inadequate immune responses and the maintenance of homeostatic tolerance. Studies have addressed and elucidated the role played by FOXP3 and Treg in countless autoimmune and infectious diseases as well as in more specific cases, such as cancer. Within this context, the present article reviews aspects of the immunoregulatory profile of FOXP3 and Treg in the management of immune homeostasis, including issues relating to pathology as well as immune tolerance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28601686/exaggerated-t-follicular-helper-cell-responses-in-lrba-deficiency-due-to-failure-of-ctla4-mediated-regulation
#17
Fayhan J Alroqi, Louis-Marie Charbonnier, Safa Baris, Ayca Kiykim, Janet Chou, Craig D Platt, Abdulrahman Algassim, Sevgi Keles, Bandar K Al Saud, Fowzan S Alkuraya, Michael Jordan, Raif S Geha, Talal A Chatila
PURPOSE: LRBA (lipopolysaccharide-responsive beige like anchor protein) and CTLA4 (cytotoxic T lymphocyte antigen 4) deficiencies give rise to overlapping phenotypes of immune dysregulation and autoimmunity, with dramatically increased frequencies of circulating T Follicular helper (cTFH) cells. We sought to determine the mechanisms of cTFH cell dysregulation in LRBA deficiency and the utility of monitoring cTFH cells as a correlate of clinical response to CTLA4-Ig therapy. METHODS: cTFH cells and other lymphocyte subpopulations were characterized...
June 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28599652/regulatory-t-cells-in-multiple-sclerosis-and-myasthenia-gravis
#18
REVIEW
K M Danikowski, S Jayaraman, B S Prabhakar
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs)...
June 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28599286/decitabine-inhibits-t-cell-proliferation-via-a-novel-tet2-dependent-mechanism-and-exerts-potent-protective-effect-in-mouse-auto-and-allo-immunity-models
#19
Xue Wang, Jun Wang, Yong Yu, Tonghui Ma, Ping Chen, Bing Zhou, Ran Tao
Multiple sclerosis (MS) is an autoimmune disease characterized by the dysregulated immune response including innate and adaptive immune responses. Increasing evidence has proven the importance of epigenetic modification in the progression of MS. Recent studies revealed that low-dose decitabine (Dec, 5-Aza-2'-deoxycytidine), which incorporates into replicating DNA and inhibits DNA methylation, could prevent experimental autoimmune encephalomyelitis (EAE) development by increasing the number of regulatory T cells (Tregs)...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598443/ash1l-and-lnc-smad3-coordinate-smad3-locus-accessibility-to-modulate-itreg-polarization-and-t-cell-autoimmunity
#20
Meng Xia, Juan Liu, Shuxun Liu, Kun Chen, Hongyu Lin, Minghong Jiang, Xiaoqing Xu, Yiquan Xue, Wei Liu, Yan Gu, Xiang Zhang, Zhiqing Li, Lin Yi, Youcun Qian, Chen Zhou, Ru Li, Xuan Zhang, Zhanguo Li, Xuetao Cao
Regulatory T (Treg) cells are important for the maintenance of immune homoeostasis and prevention of autoimmune diseases. Epigenetic modifications have been reported to modulate autoimmunity by altering Treg cell fate. Here we show that the H3K4 methyltransferase Ash1l facilitates TGF-β-induced Treg cell polarization in vitro and protects mice from T cell-mediated colitis in vivo. Ash1l upregulates Smad3 expression by directly targeting Smad3 promoter to increase local H3K4 trimethylation. Furthermore, we identify an lncRNA, namely lnc-Smad3, which interacts with the histone deacetylase HDAC1 and silences Smad3 transcription...
June 9, 2017: Nature Communications
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