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https://www.readbyqxmd.com/read/28537894/intratumoral-depletion-of-regulatory-t-cells-using-cd25-targeted-photodynamic-therapy-in-a-mouse-melanoma-model-induces-antitumoral-immune-responses
#1
Dong Sun Oh, Heegon Kim, Ji Eun Oh, Hi Eun Jung, Yun Soo Lee, Ji-Ho Park, Heung Kyu Lee
Tumor immunotherapy aims to overcome the immunosuppressive microenvironment within tumors, and various approaches have been developed. Tumor-associated T regulatory cells (Tregs) suppress the activation and expansion of tumor antigen-specific effector T cells, thus, providing a permissive environment for tumor growth. Therefore, optimal strategies need to be established to deplete tumor-infiltrated Tregs because systemic depletion of Tregs can result in reduced anti-tumor effector cells and autoimmunity. Here, to selectively deplete Tregs in tumors, we intratumorally injected anti-CD25 antibodies conjugated to Chlorin e6 (Ce6), a photosensitizer that absorbs light to generate reactive oxygen species...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534936/forsythoside-a-exerts-an-anti-endotoxin-effect-by-blocking-the-lps-tlr4-signaling-pathway-and-inhibiting-tregs-in-vitro
#2
Xiao-Yan Zeng, Wei Yuan, Lin Zhou, Shi-Xiu Wang, Yong Xie, Ying-Jun Fu
Endotoxins, also referred to as lipopolysaccharides (LPS), are powerful immunostimulators involved in a number of severe diseases. Forsythoside A (FTA), a monomer of phenethyl alcohol glycosides extracted from Forsythia suspensa, has been shown to possess anti-bacterial and immunomodulatory properties. However, it is currently not known whether FTA can counter the adverse effects of endotoxins. We investigated the effect of FTA on LPS-stimulated RAW264.7 cells and primary lymphocytes to determine its molecular mechanism of action...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534310/combination-immunotherapy-for-type-1-diabetes
#3
REVIEW
Robert N Bone, Carmella Evans-Molina
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28533488/tim-3-inhibits-low-density-lipoprotein-induced-atherogenic-responses-in-human-umbilical-vein-endothelial-cells
#4
Ming-Ke Qiu, Song-Cun Wang, Yong Tang, Chang Pan, Yang Wang, Shu-Qing Wang, Zhi-Wei Quan, Jing-Min Ou
Endothelial injury and dysfunction followed by endothelial activation and inflammatory cell recruitment are factors contributing to the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein (ox-LDL) promotes inflammation during atherogenesis and lipid deposition in the arterial wall. We observed that stimulation of human umbilical vein endothelial cells (HUVECs) with ox-LDL activated pro-inflammatory cytokine production and apoptosis, inhibited cell migration, and upregulated T-cell immunoglobulin and mucin domain 3 (Tim-3) expression...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28533380/ccr8-foxp3-treg-cells-as-master-drivers-of-immune-regulation
#5
Yiftah Barsheshet, Gizi Wildbaum, Eran Levy, Alon Vitenshtein, Chika Akinseye, Jeremy Griggs, Sergio A Lira, Nathan Karin
The current study identifies CCR8(+) regulatory T cells (Treg cells) as drivers of immunosuppression. We show that in human peripheral blood cells, more than 30% of Treg up-regulate CCR8 following activation in the presence of CCL1. This interaction induces STAT3-dependent up-regulation of FOXp3, CD39, IL-10, and granzyme B, resulting in enhanced suppressive activity of these cells. Of the four human CCR8 ligands, CCL1 is unique in potentiating Treg cells. The relevance of these observations has been extended using an experimental model of multiple sclerosis [experimental autoimmune encephalomyelitis, (EAE)] and a stabilized version of mouse CCL1 (CCL1-Ig)...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28533230/deletion-of-pikfyve-alters-alveolar-macrophage-populations-and-exacerbates-allergic-inflammation-in-mice
#6
Takumi Kawasaki, Kosuke Ito, Haruhiko Miyata, Shizuo Akira, Taro Kawai
Alveolar macrophages (AMs) are specialized tissue-resident macrophages that orchestrate the immune responses to inhaled pathogens and maintain organ homeostasis of the lung. Dysregulation of AMs is associated with allergic inflammation and asthma. Here, we examined the role of a phosphoinositide kinase PIKfyve in AM development and function. Mice with conditionally deleted PIKfyve in macrophages have altered AM populations. PIKfyve deficiency results in a loss of AKT activation in response to GM-CSF, a cytokine critical for AM development...
May 22, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28531229/protein-kinase-c-theta-is-dispensable-for-suppression-mediated-by-cd25-cd4-regulatory-t-cells
#7
Kerstin Siegmund, Nikolaus Thuille, Katarzyna Wachowicz, Natascha Hermann-Kleiter, Gottfried Baier
The activation of conventional T cells upon T cell receptor stimulation critically depends on protein kinase C theta (PKCθ). However, its role in regulatory T (Treg) cell function has yet to be fully elucidated. Using siRNA or the potent and PKC family-selective pharmacological inhibitor AEB071, we could show that murine Treg-mediated suppression in vitro is independent of PKCθ function. Likewise, Treg cells of PKCθ-deficient mice were fully functional, showing a similar suppressive activity as wild-type CD25+CD4+ T cells in an in vitro suppression assay...
2017: PloS One
https://www.readbyqxmd.com/read/28530243/corrigendum-neuronal-ifn-beta-induced-pi3k-akt-foxa1-signalling-is-essential-for-generation-of-foxa1-treg-cells
#8
Yawei Liu, Andrea Marin, Patrick Ejlerskov, Louise Munk Rasmussen, Marco Prinz, Shohreh Issazadeh-Navikas
This corrects the article DOI: 10.1038/ncomms14709.
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529840/adoptive-cell-therapy-with-tregs-to-improve-transplant-outcomes-the-promise-and-the-stumbling-blocks
#9
Mohamed B Ezzelarab, Angus W Thomson
The contribution of regulatory T cells (Treg) to the induction and maintenance of tolerance is well-recognized in rodents and may contribute to long-term human organ allograft survival. The therapeutic efficacy of adoptively-transferred Treg in promoting tolerance to organ allografts is well-recognized in mouse models. Early phase 1/2 clinical studies of Treg therapy have been conducted in patients with type-1 (autoimmune) diabetes and refractory Crohn's disease, and for inhibition of graft-versus-host disease following bone marrow transplantation with proven safety...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28528914/systemic-sclerosis-dermal-fibroblasts-suppress-th1-cytokine-production-via-galectin-9-overproduction-due-to-fli1-deficiency
#10
Ryosuke Saigusa, Yoshihide Asano, Kouki Nakamura, Megumi Hirabayashi, Shunsuke Miura, Takashi Yamashita, Takashi Taniguchi, Yohei Ichimura, Takehiro Takahashi, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato
Dermal fibroblasts promote skin-localized transdifferentiation of Tregs to Th2-like cells in systemic sclerosis (SSc). However, the entire effect of SSc dermal fibroblasts on immune cells still remains unknown. Since galectin-9 induces Th2 cytokine-predominant immune imbalance by negatively regulating Th1/Th17 cells in inflammatory diseases, we investigated the contribution of galectin-9 to Th immune balance in SSc lesional skin. We utilized human clinical samples and Fli1(+/-) mice because Fli1 deficiency induces SSc-like phenotypes in various cell types...
May 18, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28527887/mst1-deficiency-promotes-b-cell-responses-by-cd4-t-cell-derived-il-4-resulting-in-hypergammaglobulinemia
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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