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https://www.readbyqxmd.com/read/29783736/revisiting-cd28-superagonist-tgn1412-as-potential-therapeutic-for-pediatric-b-cell-leukemia-a-review
#1
REVIEW
Katelyn E Brown
Pediatric acute lymphoblastic leukemia (ALL) represents the most common pediatric cancer diagnosis, with numbers rising gradually every year. This paper proposes a novel therapeutic agent for pediatric ALL on the basis of a failed clinical drug trial in 2006. TGN1412 was a promising therapeutic agent that yielded outstanding results in both in vitro studies and animal trials. It is a CD28 superagonist monoclonal antibody that activates T regulatory (TReg ) cells in the absence of costimulation of the T cell receptor (TCR) by an antigen-presenting cell...
May 19, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29775896/dysregulated-network-of-mirnas-involved-in-the-pathogenesis-of-multiple-sclerosis
#2
REVIEW
Sanam Dolati, Faroogh Marofi, Zohreh Babaloo, Leili Aghebati-Maleki, Leila Roshangar, Majid Ahmadi, Reza Rikhtegar, Mehdi Yousefi
Multiple sclerosis (MS) is a chronic and organ-specific autoimmune disease in which immune cells act against the myelin sheath, resulting in central nervous system (CNS) damage. It has been revealed that miRNAs can play significant role in the pathogenesis of MS. These regulatory molecules lead to the activation of different signaling pathways, regulation of several transcriptional factors, influencing the differentiation of Th17 cells, development of Tregs and alteration from Th2 to Th1 response in MS. New studies have discovered that dysregulation of miRNAs may trigger abnormal immune responses leading consequently in the emergence of autoimmunity...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29774031/il-10-producing-b-cells-ability-to-induce-regulatory-t-cells-is-maintained-in-rheumatoid-arthritis
#3
Julie Mielle, Rachel Audo, Michael Hahne, Laurence Macia, Bernard Combe, Jacques Morel, Claire Daien
Despite growing evidence highlighting the relevance of increasing IL-10-producing B cells (B10+ cells) in autoimmune diseases, their functions in patients are still unknown. The aim of this study was to evaluate the functions of CpG-induced B10+ cells isolated from healthy controls (HC) and rheumatoid arthritis (RA) patients, on naïve T cell differentiation. We demonstrated that CpG-induced B10+ cells from HC drove naïve T cell differentiation toward regulatory T cells (Treg cells) and IL-10-producing T cells (Tr1) through IL-10 secretion and cellular contacts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29774027/clinical-remission-of-sight-threatening-non-infectious-uveitis-is-characterized-by-an-upregulation-of-peripheral-t-regulatory-cell-polarized-towards-t-bet-and-tigit
#4
Rose M Gilbert, Xiaozhe Zhang, Robert D Sampson, Michael R Ehrenstein, Dao X Nguyen, Mahid Chaudhry, Charles Mein, Nadiya Mahmud, Grazyna Galatowicz, Oren Tomkins-Netzer, Virginia L Calder, Sue Lightman
Background: Non-infectious uveitis can cause chronic relapsing and remitting ocular inflammation, which may require high dose systemic immunosuppression to prevent severe sight loss. It has been classically described as an autoimmune disease, mediated by pro-inflammatory Th1 and Th17 T-cell subsets. Studies suggest that natural immunosuppressive CD4+ CD25+ FoxP3+ T-regulatory cells (Tregs) are involved in resolution of inflammation and may be involved in the maintenance of clinical remission...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29772575/therapeutic-effect-of-cd4-cd25-regulatory-t-cells-amplified-in-vitro-on-experimental-autoimmune-neuritis-in-rats
#5
Feng-Jie Wang, Dan Cui, Wei-Dong Qian
BACKGROUND/AIMS: This study aimed to explore whether the adoptive transfusion of autologous CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) has a therapeutic effect on Experimental autoimmune neuritis (EAN) model rats, and it provides new experimental and theoretical bases for the immunotherapy of Guillain-Barre syndrome (GBS). METHODS: CD4+CD25+ Tregs were sorted from the spleens of rats using immunomagnetic bead separation techniques combined with flow cytometry...
May 14, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29768737/providence-of-cd25-kir-cd127-foxp3-cd8-t-cell-subset-determines-the-dynamics-of-tumor-immune-surveillance
#6
Sreeparna Chakraborty, Pushpak Bhattacharjee, Abir K Panda, Kirti Kajal, Sayantan Bose, Gaurisankar Sa
CD8+ T-regulatory cells are progressively emerging as crucial components of immune system. The previous report suggests the presence of FOXP3-positive CD8+ Treg cells, similar to CD4+ Tregs, in cancer patients which produce high levels of IL10 and TGFβ for its immunosuppressive activities. At an early stage of tumor development, we have identified a subset of FOXP3-negative CD8+ CD25+ KIR+ CD127- a Treg-like subset which is essentially IFNγ-positive. However, this early induced CD8+ CD25+ CD127- T cell subset certainly distinct from the IFNγ+ CD8+ T-effecter cells...
May 16, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29760692/il17-il17ra-as-a-novel-signaling-axis-driving-mesenchymal-stem-cell-therapeutic-function-in-experimental-autoimmune-encephalomyelitis
#7
Mónica Kurte, Patricia Luz-Crawford, Ana María Vega-Letter, Rafael A Contreras, Gautier Tejedor, Roberto Elizondo-Vega, Luna Martinez-Viola, Catalina Fernández-O'Ryan, Fernando E Figueroa, Christian Jorgensen, Farida Djouad, Flavio Carrión
The therapeutic effect of mesenchymal stem cells (MSCs) in multiple sclerosis (MS) and the experimental autoimmune encephalomyelitis (EAE) model has been well described. This effect is, in part, mediated through the inhibition of IL17-producing cells and the generation of regulatory T cells. While proinflammatory cytokines such as IFNγ, TNFα, and IL1β have been shown to enhance MSCs immunosuppressive function, the role of IL17 remains poorly elucidated. The aim of this study was, therefore, to investigate the role of the IL17/IL17R pathway on MSCs immunoregulatory effects focusing on Th17 cell generation in vitro and on Th17-mediated EAE pathogenesis in vivo ...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29756667/soluble-fgl2-restricts-autoimmune-hepatitis-progression-via-suppressing-tc17-and-conventional-cd8-t-cells-function
#8
Guo Ai, Weiming Yan, Haijing Yu, Fang Xiao, Dong Xi, Ke Ma, Jiaquan Huang, Xiaoping Luo, Xiaoyang Wan, Qin Ning
OBJECTIVE: Autoimmune hepatitis (AIH) is an inflammatory disease caused by aberrant immune response to hepatic self-antigens in which regulatory T cells (Tregs) are critical to maintain immunosupression. Soluble form of Fibrinogen-like protein 2 (sFGL2), a novel effector molecule of Treg is rarely investigated in AIH. Here, we dissected the role of sFGL2 in the autoimmune hepatitis and its potential mechanism underlying AIH progression. METHODS: Plasma and intrahepatic sFGL2 levels, as well as Treg cells were measured in both AIH patients and experimental autoimmune hepatitis (EAH) mice...
May 14, 2018: Journal of Gene Medicine
https://www.readbyqxmd.com/read/29755456/targeting-regulatory-t-cells-to-treat-patients-with-systemic-lupus-erythematosus
#9
REVIEW
Masayuki Mizui, George C Tsokos
Regulatory T cells (Tregs) are central in integration and maintenance of immune homeostasis. Since breakdown of self-tolerance is a major culprit in the pathogenesis of systemic lupus erythematosus (SLE), restoration of the immune tolerance through the manipulation of Tregs can be exploited to treat patients with SLE. New information has revealed that Tregs besides their role in suppressing the immune response are important in tissue protection and regeneration. Expansion of Tregs with low-dose IL-2 represents an approach to control the autoimmune response...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29751196/the-significance-role-of-regulatory-t-cells-in-the-persistence-of-infections-by-intracellular-bacteria
#10
REVIEW
Parisa Sabbagh, Ahmad Karkhah, Hamid Reza Nouri, Mostafa Javanian, Soheil Ebrahimpour
Regulatory T cells (Treg cells), are considered as effective immune cells playing a key role in immune response during cancers, autoimmune and infectious diseases. Regulatory T lymphocytes are divided into two main subgroups: natural Treg cells that generated during maturation in the thymus and have the suppressive activity that is critical for the establishment and maintenance of homeostasis in the body and induced Treg cells (iTreg) that are originated from naive T cells following the self-antigen recognition...
May 8, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29750331/salivary-gland-protective-regulatory-t-cell-dysfunction-underlies-female-specific-sialadenitis-in-the-nonobese-diabetic-mouse-model-of-sj%C3%A3-gren-syndrome
#11
Jennifer Y Barr, Xiaofang Wang, Portia A Kreiger, Scott M Lieberman
Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female nonobese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex-specific defect in salivary gland-protective regulatory T (Treg) cells...
May 11, 2018: Immunology
https://www.readbyqxmd.com/read/29749583/il-35-a-new-immunomodulator-in-autoimmune-rheumatic-diseases
#12
REVIEW
Lazaros I Sakkas, Athanasios Mavropoulos, Carlo Perricone, Dimitrios P Bogdanos
IL-35 is a relatively new cytokine that emerges as an important immunomodulator. IL-35 belongs to IL-12 cytokine family that includes IL-12, IL-23, IL-27, and IL-35. These cytokines are heterodimers that share subunits and their receptors also share subunits. Whereas IL-12 and IL-23 are clearly proinflammatory cytokines, the role of IL-35 is less clear. In mice, IL-35 appears to be anti-inflammatory and to protect from autoimmune inflammatory diseases. IL-35 induces the expansion of a subset of regulatory T cells (Tregs) and Bregs and mediates their suppressive function and inhibits Th17 cells...
May 11, 2018: Immunologic Research
https://www.readbyqxmd.com/read/29748000/deletion-of-the-c6orf120-gene-with-unknown-function-ameliorates-autoimmune-hepatitis-induced-by-concanavalin-a
#13
Man-Ka Zhang, Hui-Min Ma, Jian Zhang, Xin-Cheng Song, Xiao-Hui Ye, Yu-Feng Li, Yi-Fan Zhang, Ling-Ling He, Hong-Shan Wei, Xin Li
The present study was conducted to characterize the C6orf120 gene, by using C6orf120 gene-deleted rats (C6orf120- / - ), to determine its role in the development and severity of autoimmune hepatitis induced by concanavalin A (Con A), as well as the underlying mechanisms. We found that following Con A injection, C6orf120- / - rats were less susceptible to developing autoimmune hepatitis with low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) post challenge. Additionally, C6orf120 deficiency increased the frequency of cluster of differentiation (CD)4+ CD25+ Forkhead box P3+ regulatory T cells (Tregs) among intrahepatic lymphocytes, splenocytes, peripheral blood mononuclear cells, and CD4+ T in vitro...
May 2, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29743613/immune-quiescence-in-the-oral-mucosa-is-maintained-by-a-uniquely-large-population-of-highly-activated-foxp3-regulatory-t-cells
#14
Joo-Young Park, Hyunsoo Chung, Devon T DiPalma, Xuguang Tai, Jung-Hyun Park
The oral mucosa is a critical barrier tissue that protects the oral cavity against invading pathogens and foreign antigens. Interestingly, inflammation in the oral cavity is rarely observed, indicating that overt immune activation in this site is actively suppressed. Whether Foxp3+ Treg cells are involved in controlling immunity of the oral mucosa, however, is not fully understood. Here, we show that the oral mucosa is highly enriched in Foxp3+ Treg cells, and that oral mucosa Treg cells are phenotypically distinct from those of LN or spleen, as they expressed copious amounts of the tissue-retention molecule CD103 and unusually high-levels of CTLA4...
May 9, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29740452/interleukin-27-gene-therapy-prevents-the-development-of-autoimmune-encephalomyelitis-but-fails-to-attenuate-established-inflammation-due-to-the-expansion-of-cd11b-gr-1-myeloid-cells
#15
Jianmin Zhu, Jin-Qing Liu, Zhihao Liu, Lisha Wu, Min Shi, Jianchao Zhang, Jonathan P Davis, Xue-Feng Bai
Interleukin-27 (IL-27) and its subunit P28 (also known as IL-30) have been shown to inhibit autoimmunity and have been suggested as potential immunotherapeutic for autoimmune diseases such as multiple sclerosis (MS). However, the potential of IL-27 and IL-30 as immunotherapeutic, and their mechanisms of action have not been fully understood. In this study, we evaluated the efficacy of adeno-associated viral vector (AAV)-delivered IL-27 (AAV-IL-27) and IL-30 (AAV-IL-30) in a murine model of MS. We found that one single administration of AAV-IL-27, but not AAV-IL-30 completely blocked the development of experimental autoimmune encephalomyelitis (EAE)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29740445/loss-of-perp-in-t-cells-promotes-resistance-to-apoptosis-of-t-helper-17-cells-and-exacerbates-the-development-of-experimental-autoimmune-encephalomyelitis-in-mice
#16
Yan Zhou, Xiao Leng, Yan He, Yan Li, Yuan Liu, Yang Liu, Qiang Zou, Guixiu Shi, Yantang Wang
T helper 17 (Th17) cells are crucial for the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in animals. High frequency of Th17 cells and low sensitivity to activation-induced cell death (AICD) are detected in MS patients. However, the mechanisms underlying apoptosis resistance of T cells remain unclear. Perp is an apoptosis-associated target of p53 and implicated in the development of cancers. Here, we show that loss of Perp in T cells does not affect Th1, Th17, or Treg cell differentiation, but does significantly increase the resistance of Perp -/- Th17 cells to AICD and anti-Fas in Lck-Cre ×  Perp fl/fl mice by inhibiting the caspase-dependent apoptotic pathway...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29738575/adoptive-transfer-of-dendritic-cells-expressing-cd11c-reduces-the-immunological-response-associated-with-experimental-colitis-in-balb-c-mice
#17
Lisiery N Paiatto, Fernanda G D Silva, Áureo T Yamada, Wirla M S C Tamashiro, Patricia U Simioni
INTRODUCTION: In addition to conventional therapies, several new strategies have been proposed for modulating autoimmune diseases, including the adoptive transfer of immunological cells. In this context, dendritic cells (DCs) appear to be one of the most promising treatments for autoimmune disorders. The present study aimed to evaluate the effects of adoptive transfer of DCs obtained from both naïve and ovalbumin (OVA)-tolerant mice on the severity of TNBS induced colitis and analyze the eventual protective mechanisms...
2018: PloS One
https://www.readbyqxmd.com/read/29737401/transplantation-of-adipose-tissue-derived-stem-cells-ameliorates-autoimmune-pathogenesis-in-mrl-lpr-mice-modulation-of-the-balance-between-th17-and-treg
#18
W Zhang, Y-L Feng, C-Y Pang, F-A Lu, Y-F Wang
BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells characterized by immunomodulatory properties and are therefore considered a promising tool for the treatment of autoimmune diseases. In this study, we aimed to investigate whether transplantation of adipose tissue-derived stem cells (ADSCs) affects the autoimmune pathogenesis in MRL/lpr mice. METHODS: Fifteen 12-week-old MRL/lpr mice were randomly divided into three groups: ADSC, cyclophosphamide (CTX), and control groups, with five mice in each group...
May 8, 2018: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/29730990/time-resolved-transcriptome-and-proteome-landscape-of-human-regulatory-t-cell-treg-differentiation-reveals-novel-regulators-of-foxp3
#19
Angelika Schmidt, Francesco Marabita, Narsis A Kiani, Catharina C Gross, Henrik J Johansson, Szabolcs Éliás, Sini Rautio, Matilda Eriksson, Sunjay Jude Fernandes, Gilad Silberberg, Ubaid Ullah, Urvashi Bhatia, Harri Lähdesmäki, Janne Lehtiö, David Gomez-Cabrero, Heinz Wiendl, Riitta Lahesmaa, Jesper Tegnér
BACKGROUND: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood. RESULTS: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation...
May 7, 2018: BMC Biology
https://www.readbyqxmd.com/read/29728574/pathological-conversion-of-regulatory-t-cells-is-associated-with-loss-of-allotolerance
#20
Jing Hua, Takenori Inomata, Yihe Chen, William Foulsham, William Stevenson, Tina Shiang, Jeffrey A Bluestone, Reza Dana
CD4+ CD25+ Foxp3+ Regulatory T cells (Tregs) play a critical role in immune tolerance. The plasticity and functional adaptability of Tregs in an inflammatory microenvironment has been demonstrated in autoimmunity. Here, using a double transgenic mouse model that permits Foxp3 lineage tracing, we investigated the phenotypic plasticity of Foxp3+ Tregs in a well-characterized murine model of corneal transplantation. In order to subvert the normal immune privilege of the cornea and foster an inflammatory milieu, host mice were exposed to desiccating stress prior to transplantation...
May 4, 2018: Scientific Reports
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