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https://www.readbyqxmd.com/read/28527887/mst1-deficiency-promotes-b-cell-responses-by-cd4-t-cell-derived-il-4-resulting-in-hypergammaglobulinemia
#1
Eunchong Park, Myun Soo Kim, Ju Han Song, Kyung Min Cho, Kyung-Hye Roh, Rana Lee, Tae Sung Kim
MST1 deficiency causes T and B cell lymphopenia, resulting in combined immunodeficiency. However, MST1-deficient patients also exhibit autoimmune-like symptoms such as hypergammaglobulinemia and autoantibody production. Recent studies have shown that the autoimmune responses observed in MST1-deficient patients were most likely attributable to defective regulatory T (Treg) cells instead of intrinsic signals in MST1-lacking B cells. Nevertheless, it is not determined how MST1 deficiency in T cells breaks B cell tolerance and causes systemic autoimmune-like phenotypes...
May 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28524239/oral-contraceptive-pills-risky-or-protective-in-case-of-trichinella-spiralis-infection
#2
Marwa A Hasby Saad, Dina A Radi, Eiman A Hasby
AIM: to investigate how Trichinella spiralis infection can be affected by contraceptive pills invivo. METHODS: included six groups of female Wistar rats; healthy, Trichinella infected, receiving combined contraceptive pills (COCPs), receiving progestin only pills (POPs), infected receiving COCPs and infected receiving POPs. Parasite burden was measured (two gender worm counts, gravidity, larvae/muscle and RCI). Histopathological examination, immunohistochemical detection of C-kit mast cells & Foxp3+ T-reg...
May 19, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28523463/immature-exosomes-derived-from-microrna-146a-overexpressing-dendritic-cells-act-as-antigen-specific-therapy-for-myasthenia-gravis
#3
Weifan Yin, Song Ouyang, Zhaohui Luo, Qiuming Zeng, Bo Hu, Liqun Xu, Yuan Li, Bo Xiao, Huan Yang
Myasthenia gravis (MG) is a neurological autoimmune disease characterized by fluctuating weakness of certain voluntary muscles. Current treatments for MG are largely directed at suppressing the whole immune system by using immunosuppressants or glucocorticoids and often cause several side effects. The ideal therapeutic methods for MG should suppress aberrant immunoactivation specifically, while retaining normal function of the immune system. In this study, we first produced exosomes from microRNA-146a overexpressing dendritic cells (DCs)...
May 18, 2017: Inflammation
https://www.readbyqxmd.com/read/28523202/identification-of-a-novel-alternatively-spliced-form-of-inflammatory-regulator-swap-70-like-adapter-of-t-cells
#4
Marie Hashimoto, Jun-Ichi Nagao, Shojiro Ikezaki, Sonoko Tasaki, Ken-Ichi Arita-Morioka, Yuka Narita, Tamaki Cho, Kenji Yuasa, Amnon Altman, Yoshihiko Tanaka
Activation of naive CD4(+) T cells results in the development of several distinct subsets of effector Th cells, including Th2 cells that play a pivotal role in allergic inflammation and helminthic infections. SWAP-70-like adapter of T cells (SLAT), also known as Def6 or IBP, is a guanine nucleotide exchange factor for small GTPases, which regulates CD4(+) T cell inflammatory responses by controlling Ca(2+)/NFAT signaling. In this study, we have identified a novel alternatively spliced isoform of SLAT, named SLAT2, which lacks the region encoded by exons 2-7 of the Def6 gene...
2017: International Journal of Inflammation
https://www.readbyqxmd.com/read/28523126/transforming-growth-factor-%C3%AE-a-master-regulator-of-the-gut-microbiota-and-immune-cell-interactions
#5
REVIEW
David Bauché, Julien C Marie
The relationship between host organisms and their microbiota has co-evolved towards an inter-dependent network of mutualistic interactions. This interplay is particularly well studied in the gastrointestinal tract, where microbiota and host immune cells can modulate each other directly, as well as indirectly, through the production and release of chemical molecules and signals. In this review, we define the functional impact of transforming growth factor-beta (TGF-β) on this complex interplay, especially through its modulation of the activity of local regulatory T cells (Tregs), type 17 helper (Th17) cells, innate lymphoid cells (ILCs) and B cells...
April 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28522406/therapeutic-effect-of-cryptotanshinone-on-experimental-rheumatoid-arthritis-through-downregulating-p300-mediated-stat3-acetylation
#6
Ying Wang, Chun Zhou, Hui Gao, Cuixian Li, Dong Li, Peiqing Liu, Min Huang, Xiaoyan Shen, Liang Liu
BACKGROUND AND PURPOSE: The balance between T helper 17 (Th17) cells and regulatory T (Treg) cells, plays a critical role in rheumatoid arthritis (RA). The differentiation of Th17 cells requires the activation of STAT3, which determines the balance of Th17/Treg. Here, we investigated the therapeutic effect of Cryptotanshinone (CTS) on collagen induced mouse arthritis and explored the underlying mechanisms. EXPERIMENTAL APPROACH: Arthritis was induced in DBA/1 mice with bovine collagen type II and complete Freund's adjuvant...
May 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28522286/increased-proportions-of-functionally-impaired-regulatory-t-cell-subsets-in-systemic-sclerosis
#7
Emese Ugor, Diána Simon, Giovanni Almanzar, Ramóna Pap, József Najbauer, Péter Németh, Péter Balogh, Martina Prelog, László Czirják, Tímea Berki
Treg abnormalities have been implicated in the pathogenesis of systemic sclerosis (SSc). Treg subpopulations and their cytokines, IL-10 and TGF-β in the peripheral blood of early stage SSc patients were investigated. We hypothesized that epigenetically regulated methylation of the FOXP3 promoter and enhancer regions are altered in Tregs of SSc patients, which might be involved in the T cell imbalance. CD4+CD25+Foxp3+CD127- Treg cells were significantly elevated in patients with diffuse cutaneous SSc and in patients with anti-Scl-70/RNA-Pol-III autoantibody positivity and with lung fibrosis...
May 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28521478/enhancement-of-antitumor-immunity-by-combination-of-anti-ctla-4-antibody-and-radioimmunotherapy-through-the-suppression-of-tregs
#8
Cheol-Hun Son, Jaeho Bae, Hong-Rae Lee, Kwangmo Yang, You-Soo Park
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed during cluster of differentiation (CD)4+ T-cell activation and terminates immune responses by interrupting CD28-enhanced activation. In addition, CTLA-4 is known to be constitutively expressed in regulatory T-cells (Tregs) and to contribute to immune suppression by enhancing the suppressive function of Tregs. However, the molecular mechanisms underlying CTLA-4-mediated Treg suppression remains incompletely understood. Furthermore, it is uncertain whether the in vivo immune suppressive functions of CTLA-4 are mediated only by a reduction in the level of conventional T-cell activity, or enhancement of Treg function...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521455/kdm3a-promotes-inhibitory-cytokines-secretion-by-participating-in-tlr4-regulation-of-foxp3-transcription-in-lung-adenocarcinoma-cells
#9
Yinan Li, Wei Yang, Bin Wu, Yaqing Liu, Dongbei Li, Yantong Guo, Haiying Fu, Yi Li
Toll-like receptor 4 (TLR4) is a pattern recognition receptors, a member of the Toll-like receptor family and it serves a role in innate and acquired immunity. It has previously been reported that TLR4 was overexpressed in a variety of tumor tissues and cells, including colorectal cancer, gastric cancer and ovarian cancer. In the tumor microenvironment, the TLR4 signaling pathway may be activated in order to upregulate forkhead box P3 (Foxp3) expression in regulatory T cells (Tregs), and thus enhance the immunosuppressive function of Tregs...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521429/b-cells-inhibit-the-antitumor-immunity-against-an-established-murine-fibrosarcoma
#10
Andrea Maglioco, Damián G Machuca, María Noel Badano, Paula Nannini, Gabriela V Camerano, Héctor Costa, Roberto Meiss, Raúl A Ruggiero, Mirta Giordano, Graciela I Dran
Despite the classic role of B cells in favoring the immune response, an inhibitory action of B lymphocytes in tumor immunity has emerged in certain studies. In methylcolanthrene-induced murine fibrosarcoma (MCC), the loss of immunogenicity and the establishment of tolerance are paralleled by systemic immune suppression and the appearance of B(+)IL-10(+) cells in tumor-draining lymph nodes. The present study aimed to assess the role of the B(+)IL-10(+) cell population in the immune evasion and tolerance induced by MCC through the depletion of B cells in mice at various times of tumor progression: Prior to or subsequent to tumor implantation...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521292/tumor-infiltrating-immune-cells-and-prognosis-in-gastric-cancer-a-systematic-review-and-meta-analysis
#11
Wen Jiang, Ke Liu, Qing Guo, Ji Cheng, Liming Shen, Yinghao Cao, Jing Wu, Jianguo Shi, Heng Cao, Bo Liu, Kaixiong Tao, Guobin Wang, Kailin Cai
Tumor-infiltrating immune cells are a pivotal component of the tumor microenvironment (TME), but their indicative role remains poorly defined. A meta-analysis was performed to reveal the prognostic efficiency of tumor-infiltrating immune cells in gastric cancer (GC). By searching PubMed and Embase, we identified a total of 35 eligible articles that involved 4888 patients. Random or fixed effect models were employed to extract pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Our results indicated that high CD3+ lymphocyte infiltration in all the locations (AG), the tumor nest (TN), and the tumor stroma (TS) predicted better overall survival (OS) (HR=0...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28520232/human-ipsc-msc-derived-xenografts-modulate-immune-responses-by-inhibiting-the-cleavage-of-caspases
#12
Cheng-Lin Li, Yun Leng, Bin Zhao, Chang Gao, Fei-Fei Du, Ning Jin, Qi-Zhou Lian, Shuang-Yue Xu, Guo-Liang Yan, Jun-Jie Xia, Guo-Hong Zhuang, Qing-Ling Fu, Zhong-Quan Qi
Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs. However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear. We established an iPSC-MSC-transplanted host versus graft reaction mouse model using subcapsular kidney injection. Th1, Th2, regulatory T cells (Treg), and Th17 phenotypes and their cytokines were investigated in vivo and in vitro. The role of caspases and the soluble factors involved in the effects of MSCs were examined...
May 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28515363/lung-cd103-dendritic-cells-restrain-allergic-airway-inflammation-through-il-12-production
#13
Laura Conejero, Sofía C Khouili, Sarai Martínez-Cano, Helena M Izquierdo, Paola Brandi, David Sancho
DCs are necessary and sufficient for induction of allergic airway inflammation. CD11b+ DCs direct the underlying Th2 immunity, but debate surrounds the function of CD103+ DCs in lung immunity and asthma after an allergic challenge. We challenged Batf3-/- mice, which lacked lung CD103+ DCs, with the relevant allergen house dust mite (HDM) as a model to ascertain their role in asthma. We show that acute and chronic HDM exposure leads to defective Th1 immunity in Batf3-deficient mice. In addition, chronic HDM challenge in Batf3-/- mice results in increased Th2 and Th17 immune responses and exacerbated airway inflammation...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515282/talin-plays-a-critical-role-in-the-maintenance-of-the-regulatory-t-cell-pool
#14
Jane E Klann, Kelly A Remedios, Stephanie H Kim, Patrick J Metz, Justine Lopez, Lauren A Mack, Ye Zheng, Mark H Ginsberg, Brian G Petrich, John T Chang
Talin, a cytoskeletal protein essential in mediating integrin activation, has been previously shown to be involved in the regulation of T cell proliferation and function. In this study, we describe a role for talin in maintaining the homeostasis and survival of the regulatory T (Treg) cell pool. T cell-specific deletion of talin in Tln1(fl/fl)Cd4(Cre) mice resulted in spontaneous lymphocyte activation, primarily due to numerical and functional deficiencies of Treg cells in the periphery. Peripheral talin-deficient Treg cells were unable to maintain high expression of IL-2Rα, resulting in impaired IL-2 signaling and ultimately leading to increased apoptosis through downregulation of prosurvival proteins Bcl-2 and Mcl-1...
May 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28514770/mm-bmscs-induce-na%C3%A3-ve-cd4-t-lymphocytes-dysfunction-through-fibroblast-activation-protein-%C3%AE
#15
Xiaofei Wu, Yadan Wang, Jian Xu, Ting Luo, Jun Deng, Yu Hu
BACKGROUND: The tumor microenvironment plays a major role in multiple myelomas (MM). MM-BMSCs (bone marrow mesenchymal stromal cells) can support tumor growth and immune surveillance escape. On the other hand, fibroblast activation protein α, expressed by cancer stroma cells including BMSCs, has been shown to potentiate epithelial cancers growth and immune suppression. RESULTS: MM-BMSC inhibited proliferation of T cells (P = 0.0138), promoted senescence of T cells (P < 0...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512288/lactic-acid-bacteria-specific-induction-of-cd4-foxp3-t-cells-ameliorates-shrimp-tropomyosin-induced-allergic-response-in-mice-via-suppression-of-mtor-signaling
#16
Linglin Fu, Jixiang Peng, Shushu Zhao, Yan Zhang, Xiurong Su, Yanbo Wang
The beneficial effects of probiotics have been described in allergic sensitization and diseases; however, many questions remain unanswered, such as characteristics of the most effective strains in modulation of allergic responses and how orally administered probiotics affect the systemic immune system. In the present work, oral administration of five lactic acid bacteria strains showed variable effects on protection against the allergic reaction in a mouse model of food allergy to shrimp tropomyosin (ST). The most effective anti-allergic strain, Bacillus coagulans 09...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28512255/immune-consequences-of-penfluridol-treatment-associated-with-inhibition-of-glioblastoma-tumor-growth
#17
Alok Ranjan, Stephen Wright, Sanjay K Srivastava
Glioblastoma is the most common and lethal brain tumor associated with only 12% median survival rate of patients. Despite the development of advanced surgical, radiation or use of combinations of anti-cancer drugs, treatment for glioblastoma patients is still a challenge. The major contributing factor in glioblastoma progression and resistive nature is its ability to evade the immune surveillance. Hence, modulating the immune system in glioblastoma tumors could be an important strategy for anticancer therapeutics...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28511719/interleukin-10-producing-lag3-regulatory-t-cells-are-associated-with-disease-activity-and-abatacept-treatment-in-rheumatoid-arthritis
#18
Shinichiro Nakachi, Shuji Sumitomo, Yumi Tsuchida, Haruka Tsuchiya, Masanori Kono, Rika Kato, Keiichi Sakurai, Norio Hanata, Yasuo Nagafuchi, Shoko Tateishi, Hiroko Kanda, Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
BACKGROUND: Regulatory T cells (Tregs) play a role in the suppression of inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify the function of human IL-10-producing CD4(+)CD25(-)LAG3(+) T cells (LAG3(+) Tregs) and their association with rheumatoid arthritis (RA). METHODS: LAG3(+) Tregs of human peripheral blood mononuclear cells (PBMCs) were cultured with B cells and follicular helper T cells to examine antibody suppression effects...
May 16, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28507813/deep-exploration-of-the-immune-infiltrate-and-outcome-prediction-in-testicular-cancer-by-quantitative-multiplexed-immunohistochemistry-and-gene-expression-profiling
#19
Peter J Siska, Romany A N Johnpulle, Alice Zhou, Jennifer Bordeaux, Ju Young Kim, Bashar Dabbas, Naveen Dakappagari, Jeffrey C Rathmell, W Kimryn Rathmell, Alicia K Morgans, Justin M Balko, Douglas B Johnson
Platinum-based chemotherapy is usually curative for patients with testicular germ cell tumors (TGCT), but a subset of patients experience disease progression and poor clinical outcomes. Here, we tested whether immune profiling of TGCT could identify novel prognostic markers and therapeutic targets for this patient cohort. We obtained primary and metastatic TGCT samples from one center. We performed immune profiling using multiplexed fluorescence immunohistochemistry (FIHC) for T-cell subsets and immune checkpoints, and targeted gene expression profiling (Nanostring nCounter Immune panel)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#20
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
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