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https://www.readbyqxmd.com/read/28525959/challenges-and-opportunities-in-targeting-the-cd28-ctla-4-pathway-in-transplantation-and-autoimmunity
#1
Rebecca L Crepeau, Mandy L Ford
Introduction T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. Areas Covered This review discusses past, current and future biological therapies that have been utilized to block the CD28/CTLA-4 cosignaling pathway in the settings of autoimmunity and transplantation, as well the challenges facing successful implementation of these therapies...
May 19, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28523463/immature-exosomes-derived-from-microrna-146a-overexpressing-dendritic-cells-act-as-antigen-specific-therapy-for-myasthenia-gravis
#2
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/28522600/frontline-science-nasal-epithelial-gm-csf-contributes-to-tlr5-mediated-modulation-of-airway-dendritic-cells-and-subsequent-iga-response
#3
Yuan Cao, Ejuan Zhang, Jingyi Yang, Yi Yang, Jie Yu, Yang Xiao, Wei Li, Dihan Zhou, Yaoming Li, Bali Zhao, Hu Yan, Mengji Lu, Maohua Zhong, Huimin Yan
Flagellin, as a TLR5 agonist, is an established mucosal adjuvant for enhancing mucosal IgA responses by i.n. immunization. Nasal epithelial cells (NECs) are the first sentinel cells to be exposed to antigen and adjuvant in i.n. immunization, and it is suggested that they play an important role in the mucosal adjuvant activity of flagellin. However, the molecular mechanism leading to modulation and the response by flagellin-activated NECs remain unknown. We aimed to identify the soluble mediator(s) from flagellin-activated NECs that modulate the functions of airway dendritic cells (DCs) and enhance subsequent IgA response...
May 18, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28513775/adiponectin-inhibits-oxidization-induced-differentiation-of-t-helper-cells-through-inhibiting-costimulatory-cd40-and-cd80
#4
Y Xiao, T Deng, Z Shang, D Wang
Adiponectin is a multifunctional adipokine that has several oligomeric forms in the blood stream, which broadly regulates innate and acquired immunity. Therefore, in this study, we aimed to observe the differentiation of T helper (Th) cells and expression of costimulatory signaling molecules affected by adiponectin. The mRNA and protein expression levels of adiponectin and its receptors in oxidized low density lipoprotein cholesterol-treated endothelial cells were assayed by real time PCR and immunofluorescence...
May 15, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28506830/antibiotics-induced-gut-microbiota-dysbiosis-promotes-tumor-initiation-via-affecting-apc-th1-development-in-mice
#5
Chengming Xu, Banjun Ruan, Yinghao Jiang, Ting Xue, Zhenyu Wang, Huanyu Lu, Ming Wei, Shan Wang, Zicheng Ye, Dongsheng Zhai, Li Wang, Zifan Lu
Gut microbiota is critical for maintaining body immune homeostasis and thus affects tumor growth and therapeutic efficiency. Here, we investigated the link between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell transplantation, and explored the underlying mechanism. We found disruption of gut microbiota by pretreating mice with antibiotics promote tumor growth and remodeling the immune compartment within the primary tumor. Indeed, gut microbial dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor, together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as well as defective Th1 cytokines, including IFNγ, TNFα, IL12p40, and IL12p35...
May 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28505365/allograft-inflammatory-factor-1-links-t-cell-activation-interferon-response-and-macrophage-activation-in-chronic-kawasaki-disease-arteritis
#6
Anne H Rowley, Susan C Baker, Kwang-Youn A Kim, Stanford T Shulman, Amy Yang, David Arrollo, Matthew DeBerge, Shuling Han, Nicholas E S Sibinga, Adam J Pink, Edward B Thorp
Background.: Kawasaki disease (KD) is widely viewed as an acute arteritis. However, our pathologic studies show that chronic coronary arteritis can persist long after disease onset and is closely linked with arterial stenosis. Transcriptome profiling of acute KD arteritis tissues revealed upregulation of T lymphocyte, type I interferon, and allograft inflammatory factor-1 (AIF1) genes. We determined whether these immune responses persist in chronic KD arteritis, and we investigated the role of AIF1 in these responses...
May 15, 2017: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/28503991/platelet-concentrates-modulate-myeloid-dendritic-cell-immune-responses
#7
Katrina K Ki, Helen M Faddy, Robert L Flower, Melinda M Dean
Platelet transfusion has been reported to modulate the recipients' immune system. To date, the precise mechanism(s) driving poor patient outcomes (e.g., increased rate of mortality, morbidity, infectious complications and prolonged hospital stays) following platelet transfusion are largely undefined. To determine the potential for platelet concentrates (PC) to modulate responses of crucial immune regulatory cells, a human in vitro whole blood model of transfusion was established. Maturation and activation of human myeloid dendritic cells (mDC) and the specialized subset blood DC antigen (BDCA)3(+) DC were assessed following exposure to buffy-coat derived PC at day (D)2 (fresh) and D5 (date-of-expiry)...
May 15, 2017: Platelets
https://www.readbyqxmd.com/read/28502128/belatacept-resistant-rejection-is-associated-with-cd28-memory-cd8-t-cells
#8
D V Mathews, W C Wakwe, S C Kim, M C Lowe, C Breeden, M E Roberts, A B Farris, E A Strobert, J B Jenkins, C P Larsen, M L Ford, R Townsend, A B Adams
Recently newer therapies have been designed to more specifically target rejection in an effort to improve efficacy and limit unwanted toxicity. Belatacept, a CD28-CD80/86 specific reagent is associated with superior patient survival and graft function than traditional therapy but its adoption as a mainstay immunosuppressive therapy has been tempered by increased rejection rates. It is essential that the underlying mechanisms associated with this rejection be elucidated before belatacept is more widely employed...
May 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28497586/r-ras-deficiency-does-not-affect-papain-induced-ige-production-in-mice
#9
Laura Kummola, Zsuzsanna Ortutay, Maria Vähätupa, Stuart Prince, Hannele Uusitalo-Järvinen, Tero A H Järvinen, Ilkka S Junttila
INTRODUCTION: R-Ras GTPase has recently been implicated in the regulation of immune functions, particularly in dendritic cell (DC) maturation, immune synapse formation, and subsequent T cell responses. METHODS: Here, we investigated the role of R-Ras in allergen-induced immune response (type 2 immune response) in Rras deficient (R-Ras KO) and wild type (WT) mice. RESULTS: Initially, we found that the number of conventional DC's in the lymph nodes (LNs) was reduced in R-Ras KO mice...
May 11, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28495139/high-yield-primary-microglial-cultures-using-granulocyte-macrophage-colony-stimulating-factor-from-embryonic-murine-cerebral-cortical-tissue
#10
Adam C Yu, Sarah E Neil, Jacqueline A Quandt
BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28494936/functional-analysis-of-dendritic-cells-generated-from-t-ipscs-from-cd4-t-cell-clones-of-sj%C3%A3-gren-s-syndrome
#11
Mana Iizuka-Koga, Hiromitsu Asashima, Miki Ando, Chen-Yi Lai, Shinji Mochizuki, Mahito Nakanishi, Toshinobu Nishimura, Hiroto Tsuboi, Tomoya Hirota, Hiroyuki Takahashi, Isao Matsumoto, Makoto Otsu, Takayuki Sumida
Although it is important to clarify the pathogenic functions of T cells in human samples, their examination is often limited due to difficulty in obtaining sufficient numbers of dendritic cells (DCs), used as antigen-presenting cells, especially in autoimmune diseases. We describe the generation of DCs from induced pluripotent stem cells derived from T cells (T-iPSCs). We reprogrammed CD4+ T cell clones from a patient with Sjögren's syndrome (SS) into iPSCs, which were differentiated into DCs (T-iPS-DCs)...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28489854/functional-and-phenotypic-evaluation-of-eosinophils-from-patients-with-the-acute-form-of-paracoccidioidomycosis
#12
Fernanda Gambogi Braga, Luciana Pereira Ruas, Ricardo Mendes Pereira, Xinaida Taligare Lima, Edson Antunes, Ronei Luciano Mamoni, Maria Heloisa Souza Lima Blotta
BACKGROUND: Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM...
May 10, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28482260/increased-expression-of-tfpi-in-human-carotid-stenosis
#13
Benedicte Stavik, Sverre Holm, Sandra Espada, Nina Iversen, Bjørnar Sporsheim, Vigdis Bjerkeli, Tuva Børresdatter Dahl, Per Morten Sandset, Mona Skjelland, Terje Espevik, Grethe Skretting, Bente Halvorsen
INTRODUCTION: Tissue factor (TF) pathway inhibitor (TFPI) is the physiological inhibitor of TF induced blood coagulation and two isoforms exists, TFPIα and TFPIβ. In atherosclerotic plaques, TFPI may inhibit TF activity and thrombus formation, which is the main cause of ischemic stroke in carotid artery disease. We aimed to identify the isoforms of TFPI present in human carotid plaques and potential sources of TFPI. MATERIALS AND METHODS: Human atherosclerotic plaques from carotid endarterectomies were used for mRNA and immunohistochemistry analyses...
April 28, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28477078/memory-b-cells-and-response-to-abatacept-in-rheumatoid-arthritis
#14
Pierre Gazeau, Guillermo Carvajal Alegria, Valérie Devauchelle-Pensec, Christophe Jamin, Julie Lemerle, Boutahar Bendaoud, Wesley H Brooks, Alain Saraux, Divi Cornec, Yves Renaudineau
Abatacept is a fusion protein (CTLA4-Ig) and therapeutic molecule labeled for the treatment of rheumatoid arthritis (RA). Abatacept acts both by disrupting the CD28-mediated activation of T cells and by interacting with CD80/CD86 molecules present on antigen presenting cells such as monocytes and memory B cells. Accordingly and to evaluate clinical and biological parameters associated with response to abatacept, a retrospective monocentric study was conducted in 43 patients with RA, and the clinical response was evaluated at 6 months according to EULAR response criteria...
May 5, 2017: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/28472775/ocular-behcet-s-disease-is-associated-with-aberrant-methylation-of-interferon-regulatory-factor-8-irf8-in-monocyte-derived-dendritic-cells
#15
Yiguo Qiu, Yunyun Zhu, Hongsong Yu, Shenglan Yi, Wencheng Su, Qingfeng Cao, Gangxiang Yuan, Aize Kijlstra, Peizeng Yang
Aberrant methylation of interferon regulatory factor 8 (IRF8) has been noted in various tumors. IRF8 has also been reported to be involved in many autoimmune diseases, including Behcet's disease (BD). However, the methylation status of IRF8 in BD has not been reported. To address this issue, we investigated whether the degree of methylation of IRF8 in dendritic cells (DCs) plays a role in the development of BD. We found a lower mRNA expression and a higher methylation level of IRF8 in active ocular BD patients as compared to normal subjects and inactive patients...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466561/alcohol-abstinence-ameliorates-the-dysregulated-immune-profiles-in-patients-with-alcoholic-hepatitis-a-prospective-observational-study
#16
Wei Li, Tohti Amet, Yanyan Xing, Dennis Yang, Suthat Liangpunsakul, Puneet Puri, Patrick Kamath, Arun Sanyal, Vijay Shah, Barry Katz, Svetlana Radaeva, David Crabb, Naga Chalasani, Qigui Yu
Alcoholic hepatitis (AH) develops only in small proportion of heavy drinkers. To better understand the mechanisms underlying this disparity, we conducted a study to define the relationship between AH development and dysregulated immune responses that might be ameliorated by alcohol abstinence. Sixty-eight AH patients, 65 heavy drinking controls without liver disease (HDC), and 20 healthy controls (HC) were enrolled and followed up to 12 months. At the baseline, HDC and HC had no significant differences in their plasma levels of 38 inflammatory cytokines/chemokines measured using multiplex immunoassays...
May 2, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28466476/numerical-and-functional-defects-in-cd8-cd28-t-suppressor-lymphocytes-from-patients-with-primary-immune-thrombocytopenia
#17
Huiyuan Li, Yating Hao, Donglei Zhang, Wenjie Liu, Yang Li, Mingen Lyu, Rongfeng Fu, Feng Xue, Xiaofan Liu, Renchi Yang
Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder, and loss of immune tolerance has been implicated in ITP pathogenesis. CD8(+) CD28(-) suppressor (Ts) cells have an immunosuppression function and are involved in several autoimmune disorders. However, the role of Ts cells in ITP is currently not clear. Here, flow cytometry was used to detect the CD8(+) CD28(-) CD127(-) proportion, which was decreased in active ITP patients compared with that of controls. Function analysis showed that immunosuppression of CD8(+) CD28(-) Ts cells in ITP patients was impaired...
May 3, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28466138/a-translational-approach-from-an-animal-model-identifies-cd80-as-a-candidate-gene-for-the-study-of-bone-phenotypes-in-postmenopausal-women
#18
L Panach, E Serna, J J Tarín, A Cano, M Á García-Pérez
This study represented a translational study that first compared gene expression of B cells of BM from ovariectomized and control mice, and then analyzed some of the differentially expressed genes in women. Results showed novel genetic associations with bone phenotypes and points to the CD80 gene as relevant in postmenopausal bone loss. INTRODUCTION: Osteoporosis is a multifactorial disease with a strong genetic component. However, to date, research into osteoporosis has only been able to explain a small part of its heritability...
May 2, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28461772/pi3k-and-erk-signaling-pathways-are-involved-in-differentiation-of-monocytic-cells-induced-by-27-hydroxycholesterol
#19
Yonghae Son, Bo-Young Kim, Young Chul Park, Seong-Kug Eo, Hyok-Rae Cho, Koanhoi Kim
27-Hydroxycholesterol induces differentiation of monocytic cells into mature dendritic cells, mDCs. In the current study we sought to determine roles of the PI3K and the ERK pathways in the 27OHChol-induced differentiation. Up-regulation of mDC-specific markers like CD80, CD83 and CD88 induced by stimulation with 27OHChol was significantly reduced in the presence of LY294002, an inhibitor of PI3K, and U0126, an inhibitor of ERK. Surface expression of MHC class I and II molecules elevated by 27OHChol was decreased to basal levels in the presence of the inhibitors...
May 2017: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/28460461/tumor-regression-is-mediated-via-the-induction-of-her263-71-specific-cd8-ctl-activity-in-a-4t1-2-her2-tumor-model-no-involvement-of-cd80-in-tumor-control
#20
Sayyed Nilofar Danishmalik, Si-Hyeong Lee, Jeong-Im Sin
In the CT26/HER2 and 4T1.2/HER2 tumor models, CT26/HER2 cells form tumors that continue to grow, whereas 4T1.2/HER2 cells form tumors that eventually regress. Here, we investigated the differences in the behaviors of these two cell lines. When immune cells from 4T1.2/HER2 tumor-bearing animals were stimulated with HER2 class I peptides, they displayed a 2-fold increase in IFN-γ levels, in response to the peptides, HER263-71 and HER2342-350. In contrast, extremely high levels of antigen-non-specific IFN-γ production were observed with immune cells and sera from CT26/HER2 tumor-bearing mice...
April 18, 2017: Oncotarget
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