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https://www.readbyqxmd.com/read/29353353/peripheral-th17-treg-imbalance-in-elderly-patients-with-ischemic-stroke
#1
Sanam Dolati, Majid Ahmadi, Mohammad Khalili, Ali Akabar Taheraghdam, Homayoon Siahmansouri, Zohreh Babaloo, Leili Aghebati-Maleki, Farhad Jadidi-Niaragh, Vahid Younesi, Mehdi Yousefi
CD4+CD25+ regulatory T (Treg) cells and Th17 cells play important roles in peripheral immunity. Immune responses are main elements in the pathogenesis of ischemic stroke (IS). The contribution of Th17 cells in IS patients has not been proved, and whether the balance of Treg/Th17 cells is changed in IS patients remains unidentified. In the present study, we studied Th17 and Treg cell frequency, cytokine secretion, expression of transcription factors, and microRNAs related to Th17 and Treg cells differentiation, which is compared between IS patients and control group...
January 20, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/29352742/cambogin-suppresses-dextran-sulphate-sodium-induced-colitis-by-enhancing-treg-cell-stability-and-function
#2
Yue Lu, Na-Mi Kim, Yi-Wen Jiang, Hong Zhang, Dan Zheng, Fu-Xiang Zhu, Rui Liang, Bin Li, Hong-Xi Xu
BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of gastrointestinal tract, and the dysfunction of immune regulation plays a critical role in IBD. Reflecting the limited use of current drugs and therapies for IBD treatment, it is necessary to explore novel drugs or therapies for this disease. We investigated the effect of cambogin in a mouse model of dextran sulphate sodium (DSS)-induced colitis and whether cambogin attenuates inflammation via Treg-cell-mediated immune modulation...
January 20, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29352298/hexokinase-ii-may-be-dispensable-for-cd4-t-cell-responses-against-a-virus-infection
#3
Siva Karthik Varanasi, Ujjaldeep Jaggi, Nissim Hay, Barry T Rouse
Activation of CD4 T cells leads to their metabolic reprogramming which includes enhanced glycolysis, catalyzed through hexokinase enzymes. Studies in some systems indicate that the HK2 isoform is the most up regulated isoform in activated T cells and in this report the relevance of this finding is evaluated in an infectious disease model. Genetic ablation of HK2 was achieved in only T cells and the outcome was evaluated by measures of T cell function. Our results show that CD4 T cells from both HK2 depleted and WT animals displayed similar responses to in vitro stimulation and yielded similar levels of Th1, Treg or Th17 subsets when differentiated in vitro...
2018: PloS One
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#4
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29349658/the-il-10-producing-regulatory-b-cells-b10-cells-and-regulatory-t-cell-subsets-in-neuromyelitis-optica-spectrum-disorder
#5
Eun Bin Cho, Hye-Jin Cho, Jin Myoung Seok, Ju-Hong Min, Eun-Suk Kang, Byoung Joon Kim
B cells contribute to the pathogenesis of neuromyelitis optica (NMO) by producing Aquaporin 4-specific autoantibodies (AQP4-ab); on the other hand, there are certain B cells that suppress immune responses by producing regulatory cytokines, such as IL-10. In this study, we investigated the presence of IL-10-producing Breg cells among lymphocyte subsets. Twenty-two seropositive NMO spectrum disorder (NMOSD) patients (29 samples) and 13 healthy controls (HCs) (14 samples) were enrolled. All NMOSD patients have received one or more immunosuppressive drugs...
January 19, 2018: Neurological Sciences
https://www.readbyqxmd.com/read/29348660/generation-and-characterization-of-alloantigen-specific-regulatory-t-cells-for-clinical-transplant-tolerance
#6
James M Mathew, Jessica H Voss, Scott T McEwen, Iwona Konieczna, Arjun Chakraborty, Xuemei Huang, Jie He, Lorenzo Gallon, Richard S Kornbluth, Joseph R Leventhal
Donor-specific CD4+CD127-CD25+FOXP3+ regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination. Purified allogeneic "recipient" CD4+CD25+ Tregs were stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2, TGFβ and sirolimus (SRL)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348565/an-in-vitro-system-of-autologous-lymphocytes-culture-that-allows-the-study-of-homeostatic-proliferation-mechanisms-in-human-naive-cd4-t-cells
#7
Isaac Rosado-Sánchez, Amaia González-Magaña, María M Pozo-Balado, Inés Herrero-Fernández, María J Polaino, María M Rodríguez-Méndez, María Francisca González-Escribano, Manuel Leal, Yolanda M Pacheco
The size of peripheral T-cell pool is kept constant throughout life. However, a decline in lymphocyte numbers is a feature of several human disorders, in which fast and slow homeostatic proliferation play a crucial role. Several in vitro and in vivo models have been developed to study such processes. Nevertheless, self- and commensal- antigens, well-known triggers of homeostatic proliferation, have not been examined in these models. We have designed an in vitro culture of human T-cells exposed to rIL7 and autologous antigen-presenting cells (aAPC) that allows the simultaneous characterization of the different types of homeostatic proliferation...
January 18, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29346764/sgk1-governs-the-reciprocal-development-of-th17-and-regulatory-t-cells
#8
Chuan Wu, Zuojia Chen, Sheng Xiao, Theresa Thalhamer, Asaf Madi, Timothy Han, Vijay Kuchroo
A balance between Th17 and regulatory T (Treg) cells is critical for immune homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid-induced kinase 1 (SGK1) is critical for the development and function of Th17 cells. Here, we show that SGK1 restrains the function of Treg cells and reciprocally regulates development of Th17/Treg balance. SGK1 deficiency leads to protection against autoimmunity and enhances self-tolerance by promoting Treg cell development and disarming Th17 cells. Treg cell-specific deletion of SGK1 results in enhanced Treg cell-suppressive function through preventing Foxo1 out of the nucleus, thereby promoting Foxp3 expression by binding to Foxp3 CNS1 region...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346060/a-combination-with-probiotic-complex-zinc-and-coenzyme-q10-attenuates-autoimmune-arthritis-by-regulation-of-th17-treg-balance
#9
Seon-Young Lee, Seung Hoon Lee, JooYeon Jhun, Hyeon-Beom Seo, Kyung Ah Jung, Chul Woo Yang, Sung-Hwan Park, Mi-La Cho
Probiotic complex, zinc, and coenzyme Q10 (CoQ10) are recognized dietary supplements with an anti-inflammatory role. Although these supplementations are individually known to benefit rheumatoid arthritis (RA), there is no evidence suggesting any synergic effect. The primary goal of this study is to determine whether probiotic complex, zinc, and CoQ10 attenuate the development of collagen-induced arthritis (CIA). The combination of probiotic complex, zinc, and CoQ10 reduced CIA severity by downregulating the levels of IgG, IgG1, and IgG2a in serum...
January 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29345851/the-immunosuppressive-effects-of-cd4-cd25-regulatory-t-cells-on-dendritic-cells-in-patients-with-chronic-hepatitis-b
#10
Pei-Pei Zhou, Juan Xu, Ming-Jia Dai, Yin-Yue Shi, Gui-Ping Wu, Yuan Fang, Xue-Bing Yan
The characteristics and functions of CD4+ CD25+ regulatory T cells (Tregs) have been well defined in murine and human systems. However, the interaction or cross-talk between CD4+ CD25+ Tregs and dendritic cells (DCs) remains controversial. In this study, the effects of chronic hepatitis B (CHB) CD4+ CD25+ Tregs on the maturation and function of monocyte-derived DCs were examined. The results showed that CD4+ CD25+ render the DCs inefficient as antigen-presenting cells (APCs) despite prestimulation with CD40 ligand...
January 18, 2018: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/29345621/the-circulating-t-helper-subsets-and-regulatory-t-cells-in-patients-with-common-variable-immunodeficiency-with-no-known-monogenic-disease
#11
G Azizi, A Mirshafiey, H Abolhassani, R Yazdani, F J Ansariha, M Shaghaghi, S S Mortazavi-Jahromi, F Noorbakhsh, N Rezaei, A Aghamohammadi
BACKGROUND: Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID), characterized by heterogeneous clinical manifestations and defects in B- and T- cells. In the present study, we investigated the T helper (Th) cell subsets and regulatory T (Treg) cells, and their related cytokines and transcription factors in the CVID patients with no definite genetic diagnosis. METHODS: The study population comprised 13 CVID patients and 13 healthy controls (HC)...
January 18, 2018: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/29345574/role-of-cd73-in-disease-promising-prognostic-indicator-and-therapeutic-target
#12
Jiayin Yang, Xiaohong Liao, Jerry Yu, Ping Zhou
CD73, also known as ecto-5'-nucleotidase (eN, NT5E, EC3.13.5), is the rate-limiting enzyme for adenosine generation and is expressed on multiple cells. Its expression is significantly influenced by hypoxia and inflammatory factors. During inflammation, CD73 protects endothelial barrier function and inhibits leukocyte trafficking. CD73 also promotes M2 macrophages (anti-inflammatory phenotype). In addition, CD73 is expressed on Treg cells and mediates immune suppression through adenosine. CD73 serves as an essential regulator for the immunity and inflammation...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345428/traf3-regulation-of-inhibitory-signaling-pathways-in-b-and-t-lymphocytes-by-kinase-and-phosphatase-localization
#13
REVIEW
Alicia M Wallis, Gail A Bishop
This brief review presents current understanding of how the signaling adapter protein TRAF3 can both induce and block inhibitory signaling pathways in B and T lymphocytes, via association with kinases and phosphatases, and subsequent regulation of their localization within the cell. In B lymphocytes, signaling through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL-6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL-6R signaling...
January 17, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29344274/immunotherapy-of-patient-with-hepatocellular-carcinoma-using-cytotoxic-t-lymphocytes-ex-vivo-activated-with-tumor-antigen-pulsed-dendritic-cells
#14
Ying Wang, Xijing Yang, Yi Yu, Zenghui Xu, Yan Sun, Hui Liu, Jingbo Cheng, Min Liu, Bibo Sha, Linfang Li, Na Ding, Zhong Li, Huajun Jin, Qijun Qian
Purpose The aim of this study was to evaluate the clinical response of immunotherapy with dendritic cell-cytotoxic T lymphocytes (DC-CTLs) in patients with hepatocellular carcinoma (HCC). Method Sixty-eight patients with a confirmed diagnosis of HCC and who received follow-up until December 2015 were enrolled. We measured immune phenotypes of DCs and activated T cells using flow cytometry and clinical indexes using an electrochemiluminescence method. Results DCs exhibited up-regulation of the maturation markers CD83, CD80, CD11c, and CD86 on day8...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29344269/early-and-partial-reduction-in-cd4-foxp3-regulatory-t-cells-during-colitis-associated-colon-cancer-induces-cd4-and-cd8-t-cell-activation-inhibiting-tumorigenesis
#15
Jonadab E Olguín, Itzel Medina-Andrade, Emmanuel Molina, Armando Vázquez, Thalia Pacheco-Fernández, Rafael Saavedra, Carlos Pérez-Plasencia, Yolanda I Chirino, Felipe Vaca-Paniagua, Luis E Arias-Romero, Emma B Gutierrez-Cirlos, Sonia A León-Cabrera, Miriam Rodriguez-Sosa, Luis I Terrazas
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in women and the third in men in North America and Europe. CRC is associated with inflammatory responses in which intestinal pathology is caused by different cell populations including a T cell dysregulation that concludes in an imbalance between activated T (Tact) and regulatory T (Treg) cells. Treg cells are CD4+Foxp3+ cells that actively suppress pathological and physiological immune responses, contributing to the maintenance of immune homeostasis...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29342501/selective-activation-of-tumor-necrosis-factor-receptor-2-induces-anti-inflammatory-responses-and-alleviates-experimental-arthritis
#16
Roman Fischer, Marcel Proske, Maëlle Duffey, Hubert Stangl, George F Martinez, Nathalie Peters, Alexandra Kraske, Rainer H Straub, John R Bethea, Roland E Kontermann, Klaus Pfizenmaier
OBJECTIVES: Regulatory T cells (Tregs) modulate immune responses and can suppress the development of autoimmune diseases. Tumor necrosis factor receptor 2 (TNFR2) has been recognized as a key receptor on these cells that facilitates expansion and stabilization of CD4+ Tregs. Here, we investigated the therapeutic activity of a novel TNFR2 agonist in experimental arthritis and the role of different Treg subsets. METHODS: A novel mouse TNFR2-selective fusion protein (EHD2-sc-mTNFR2 ) was generated by genetic engineering...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29341283/mogamulizumab-induced-phosensitivity-in-patients-with-mycosis-fungoides-and-other-t-cell-neoplasms
#17
Y Masuda, K Tatsuno, S Kitano, H Miyazawa, J Ishibe, M Aoshima, T Shimauchi, T Fujiyama, T Ito, Y Tokura
BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4, and was first approved in Japan for the treatment of adult T cell leukaemia/lymphoma (ATLL), followed by cutaneous T cell lymphoma and peripheral T cell lymphoma. OBJECTIVE: To retrospectively investigate development of photosensitivity in patients with mycosis fungoides and other T cell neoplasms after treatment with Mog. METHODS: We treated 7 cutaneous lymphoma patients with Mog...
January 16, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29341118/inhibition-of-the-fgl2-fc%C3%AE-riib-riii-immunosuppressive-pathway-enhances-antiviral-t-cell-and-b-cell-responses-leading-to-clearance-of-lcmv-cl-13
#18
Olga Klingberg, Ramzi Khattar, Kaveh Farrokhi, Dario Ferri, Nataliya Yavorska, Jianhua Zhang, Hassan Sadozai, Oyedele Adeyi, Andrzej Chruscinski, Gary A Levy, Nazia Selzner
Persistent viruses evade immune detection by interfering with virus-specific innate and adaptive antiviral immune responses. Fibrinogen-Like Protein-2 (FGL2) is a potent effector molecule of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) and exerts its immunosuppressive activity following ligation to its cognate receptor, FcγRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection caused by Lymphocytic Choriomeningitis Virus Clone-13 (LCMV cl-13) was assessed in this study. Chronically infected fgl2+/+ mice had increased plasma levels of FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on macrophages and dendritic cells (DC) and impaired production of neutralizing antibody...
January 17, 2018: Immunology
https://www.readbyqxmd.com/read/29339767/regulatory-t-cells-trigger-effector-t-cell-dna-damage-and-senescence-caused-by-metabolic-competition
#19
Xia Liu, Wei Mo, Jian Ye, Lingyun Li, Yanping Zhang, Eddy C Hsueh, Daniel F Hoft, Guangyong Peng
Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical for the development of effective strategies for treating tumors and chronic infections. The molecular processes that occur in responder T cells that are suppressed by Treg cells are unclear. Here we show that human Treg cells initiate DNA damage in effector T cells caused by metabolic competition during cross-talk, resulting in senescence and functional changes that are molecularly distinct from anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to control Treg-induced effector T-cell senescence...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#20
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
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