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https://www.readbyqxmd.com/read/28102734/fibroblast-like-synoviocytes-dependent-effector-molecules-as-a-critical-mediator-for-rheumatoid-arthritis-current-status-and-future-directions
#1
Ramamoorthi Ganesan, Mahaboobkhan Rasool
Rheumatoid arthritis (RA) is a systemic-autoimmune-mediated disease characterized by synovial hyperplasia and progressive destruction of joint. Currently available biological agents and inhibitor therapy that specifically target tumor necrosis factor-α, interleukin 1β (IL-1β), IL-6, T cells, B cells, and subcellular molecules (p38 mitogen-activated protein kinase and janus kinase) cannot facilitate complete remission in all patients and are unable to cure the disease. Therefore, further potent therapeutic targets need to be identified for effective treatment and successful clinical outcomes in patients with RA...
January 19, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28102541/tgf-%C3%AE-regulation-of-encephalitogenic-and-regulatory-t-cells-in-multiple-sclerosis
#2
REVIEW
Priscilla W Lee, Mary E Severin, Amy E Lovett-Racke
Transforming growth factor-beta (TGF-β) is a pleiotropic cytokine that has been shown to influence the differentiation and function of T cells. The role that TGF-β plays in immune-mediated disease, such as multiple sclerosis (MS), has become a major area of investigation since CD4(+) T cells appear to be a major mediator of autoimmunity. This review provides an analysis of the literature on the role that TGF-β plays in the generation and regulation of encephalitogenic and regulatory T cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, as well as in T cells of MS patients...
January 19, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28101965/a-multi-hit-hypothesis-of-bullous-pemphigoid-and-associated-neurological-disease-is-hla-dqb1-03-01-a-potential-link-between-immune-privileged-antigen-exposure-and-epitope-spreading
#3
REVIEW
K T Amber, J Zikry, M Hertl
Bullous pemphigoid (BP) is the most common autoimmune blistering disease and is linked to IgG recognition of 2 hemidesmosomal antigens, that is, BP230 (BP antigen 1) and BP180 (BP antigen 2, collagen XVII). The association of BP with other systemic diseases, particularly neurocognitive diseases, provides a potential clue in the underlying pathogenesis of BP. The role of HLA-DQB1*03:01 binding to the immunogenic portion of BP180 provides a potential mechanism by which exposure to neuronal collagen BP180 may lead to cutaneous disease...
January 19, 2017: HLA
https://www.readbyqxmd.com/read/28101786/evaluation-of-t-regulatory-lymphocytes-transcription-factors-in-htlv-1-associated-myelopathy-tropical-spastic-paraparesis-ham-tsp-patients
#4
Sanaz Ahmadi Ghezeldasht, Hamed Sadeghian, Mahmoud Reza Azarpazhooh, Seyyed Ali Akbar Shamsian, Houshang Rafatpanah, Mahmood Mahmoodi, Seyyed Abdolrahim Rezaee
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an aggressive neurological disease. The CD4(+)CD25(+) T cell population plays pivotal roles in the maintenance of immunological tolerance and prevention of such autoimmune diseases. In the current study, proviral load (PVL), factor forkhead box p3 (Foxp3), and glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) gene expression and regulatory T cells (Tregs) counts of 21 HAM/TSP patients and 16 HTLV-1 healthy carriers (ACs) were measured using real-time PCR, TaqMan method, and flow cytometry...
January 18, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28101184/anti-inflammatory-effects-of-luteolin-on-experimental-autoimmune-thyroiditis-in-mice
#5
Nan Xia, Gang Chen, Min Liu, Xiaozhen Ye, Yahui Pan, Jiuyu Ge, Yanting Mao, Hongwei Wang, Jian Wang, Sijing Xie
Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease and is believed to be a predominately T cell-mediated autoimmunity. Signal transducer and activator of transcription (STAT)3 is a crucial transcription factor of T cell-mediated immunity, with key roles in the proliferation and migration of T helper (Th) cells, differentiation of Th cells into Th17 cells, and the balance between Treg cells and Th17 cells. Flavonoid luteolin has been shown to markedly inhibit Tyr705 activation/phosphorylation of STAT3 and exert anti-inflammatory effects in multiple sclerosis...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28100846/regulatory-lymphocytes-in-thyroid-orbitopathy-and-autoimmune-thyroid-diseases
#6
Marta Siomkajło, Jarosław Dybko, Jacek Daroszewski
Thyroid orbitopathy (OT), as an organ‑specific autoimmune disease, is a result of immune dysregulation leading to loss of control over inflammation directed against self‑antigens. The source of the autoreactive lymphocytes is the impairment of central tolerance as well as their induction on the periphery by modified or sequestered by that time antigens. Active suppression by the various subpopulations of regulatory lymphocytes (Lreg) acts as a counterbalance to the proinflammatory factors and is aimed at dampening pathological reaction...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100106/systemic-lupus-erythematosus-in-the-light-of-the-regulatory-effects-of-galectin-1-on-t-cell-function
#7
Á Hornung, É Monostori, L Kovács
Galectin-1 is an endogenous immunoregulatory lectin-type protein. Its most important effects are the inhibition of the differentiation and cytokine production of Th1 and Th17 cells, and the induction of apoptosis of activated T-cells. Galectin-1 has been identified as a key molecule in antitumor immune surveillance, and data are accumulating about the pathogenic role of its deficiency, and the beneficial effects of its administration in various autoimmune disease models. Initial animal and human studies strongly suggest deficiencies in both galectin-1 production and responsiveness in systemic lupus erythematosus (SLE) T-cells...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28100093/p19-targeted-abd-derived-protein-variants-inhibit-il-23-binding-and-exert-suppressive-control-over-il-23-stimulated-expansion-of-primary-human-il-17-t-cells
#8
Lucie Křížová, Milan Kuchař, Hana Petroková, Radim Osička, Marie Hlavničková, Ondřej Pelák, Jiří Černý, Tomáš Kalina, Petr Malý
Interleukin-23 (IL-23), a heterodimeric cytokine of covalently bound p19 and p40 proteins, has recently been closely associated with development of several chronic autoimmune diseases such as psoriasis, psoriatic arthritis or inflammatory bowel disease. Released by activated dendritic cells, IL-23 interacts with IL-23 receptor (IL-23R) on Th17 cells, thus promoting intracellular signaling, a pivotal step in Th17-driven pro-inflammatory axis. Here, we aimed to block the binding of IL-23 cytokine to its cell-surface receptor by novel inhibitory protein binders targeted to the p19 subunit of human IL-23...
January 19, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28100001/transplantation-tolerance-don-t-forget-about-the-b-cells
#9
REVIEW
Anita S Chong, Stella H Khiew
Establishing a state of transplantation tolerance that leads to indefinite graft survival without the need for lifelong immunosuppression has been successfully achieved in limited numbers of transplant recipients in the clinic. These successes led to studies aimed at identifying potential biomarkers that diagnose allograft tolerance and identify the patients most amenable to drug minimization, and implicated an enriched B cell signature of tolerance. The emergence of a specialized subset of regulatory B cell (Bregs) that possess immune-modulatory function in inflammation and autoimmune disease, raised the possibility that Bregs play critical roles in the promotion of transplantation tolerance and that Bregs are the underlying explanation for the B cell signature of tolerance...
January 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28098832/therapeutic-potential-of-targeting-the-th17-treg-axis-in-autoimmune-disorders
#10
REVIEW
Patrizia Fasching, Martin Stradner, Winfried Graninger, Christian Dejaco, Johannes Fessler
A disruption of the crucial balance between regulatory T-cells (Tregs) and Th17-cells was recently implicated in various autoimmune disorders. Tregs are responsible for the maintenance of self-tolerance, thus inhibiting autoimmunity, whereas pro-inflammatory Th17-cells contribute to the induction and propagation of inflammation. Distortion of the Th17/Treg balance favoring the  pro-inflammatory Th17 side is hence suspected to contribute to exacerbation of autoimmune disorders. This review aims to summarize recent data and advances in targeted therapeutic modification of the Th17/Treg-balance, as well as information on the efficacy of candidate therapeutics with respect to the treatment of autoimmune diseases...
January 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28097735/autoimmune-enteropathy-and-hepatitis-in-pediatric-heart-transplant-recipient
#11
Kimberly Lewis, Ryan Butts, J Antonio Quiros, Michelle Hudspeth, Katherine Twombley, Andrew Savage, Sally Self, Ali Burnette, Shaoli Sun
AIE is a rare disorder in children that presents with severe diarrhea and malabsorption, caused by immune-mediated damage to intestinal mucosa. AIE is often associated with various syndromes of immunodeficiency including IPEX syndrome (immune dysregulation, polyendocrinopathy and enteropathy, X-linked). Dysfunctional T regulatory cells are the source of pathology in both IPEX syndrome and AIE as they are essential in maintaining tolerance to self-antigens and eliminating autoreactive B cells. This case report describes a 10-year-old cardiac transplant and total thymectomy patient on chronic immunosuppression with tacrolimus that presented with AIE and extraintestinal manifestations of cyclical hepatitis...
January 17, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/28097204/genomics-implicates-adaptive-and-innate-immunity-in-alzheimer-s-and-parkinson-s-diseases
#12
Sarah A Gagliano, Jennie G Pouget, John Hardy, Jo Knight, Michael R Barnes, Mina Ryten, Michael E Weale
OBJECTIVES: We assessed the current genetic evidence for the involvement of various cell types and tissue types in the etiology of neurodegenerative diseases, especially in relation to the neuroinflammatory hypothesis of neurodegenerative diseases. METHODS: We obtained large-scale genome-wide association study (GWAS) summary statistics from Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). We used multiple sclerosis (MS), an autoimmune disease of the central nervous system, as a positive control...
December 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28096390/modification-of-host-dendritic-cells-by-microchimerism-derived-extracellular-vesicles-generates-split-tolerance
#13
William Bracamonte-Baran, Jonathan Florentin, Ying Zhou, Ewa Jankowska-Gan, W John Haynes, Weixiong Zhong, Todd V Brennan, Partha Dutta, Frans H J Claas, Jon J van Rood, William J Burlingham
Maternal microchimerism (MMc) has been associated with development of allospecific transplant tolerance, antitumor immunity, and cross-generational reproductive fitness, but its mode of action is unknown. We found in a murine model that MMc caused exposure to the noninherited maternal antigens in all offspring, but in some, MMc magnitude was enough to cause membrane alloantigen acquisition (mAAQ; "cross-dressing") of host dendritic cells (DCs). Extracellular vesicle (EV)-enriched serum fractions from mAAQ(+), but not from non-mAAQ, mice reproduced the DC cross-dressing phenomenon in vitro...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28096300/enhanced-suppression-of-polyclonal-cd8-25-regulatory-t-cells-via-exosomal-arming-of-antigen-specific-peptide-mhc-complexes
#14
Chuanyong Mu, Xueshu Zhang, Lu Wang, Aizhang Xu, Khawaja Ashfaque Ahmed, Xueqin Pang, Rajni Chibbar, Andrew Freywald, Jianan Huang, Yehan Zhu, Jim Xiang
Compared with CD4(+)25(+) regulatory T cells (Tregs), the mechanisms for natural, polyclonal CD8(+)25(+) Treg immune suppression have been significantly less studied. We previously showed that polyclonal T cells can acquire antigen-specific targeting activity through arming with exosomal peptide-MHC (pMHC). In this study, we assessed the suppressive effect of CD8(+)25(+) Tregs or CD8(+)25(+) Tregs armed with ovalbumin (OVA)-specific exosomes on other immune cells and OVA-specific dendritic cell (DCOVA)-stimulated antitumor immunity...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28096232/pr-957-a-selective-inhibitor-of-immunoproteasome-subunit-low-mw-polypeptide-7-attenuates-experimental-autoimmune-neuritis-by-suppressing-th17-cell-differentiation-and-regulating-cytokine-production
#15
Haijie Liu, Chunxiao Wan, Yanan Ding, Ranran Han, Yating He, Jinting Xiao, Junwei Hao
Experimental autoimmune neuritis (EAN) is a CD4(+) T cell-mediated autoimmune inflammatory demyelinating disease of the peripheral nervous system. It has been replicated in an animal model of human inflammatory demyelinating polyradiculoneuropathy, Guillain-Barré syndrome. In this study, we evaluated the therapeutic efficacy of a selective inhibitor of the immunoproteasome subunit, low-MW polypeptide 7 (PR-957) in rats with EAN. Our results showed that PR-957 significantly delayed onset day, reduced severity and shortened duration of EAN, and alleviated demyelination and inflammatory infiltration in sciatic nerves...
January 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28095433/bj-3105-a-6-alkoxypyridin-3-ol-analog-impairs-t-cell-differentiation-and-prevents-experimental-autoimmune-encephalomyelitis-disease-progression
#16
Maheshwor Timilshina, Youra Kang, Ishmit Dahal, Zhiwei You, Tae-Gyu Nam, Keuk-Jun Kim, Byeong-Seon Jeong, Jae-Hoon Chang
CD4+ T cells are essential in inflammation and autoimmune diseases. Interferon-γ (IFN-γ) secreting T helper (Th1) and IL-17 secreting T helper (Th17) cells are critical for several autoimmune diseases. To assess the inhibitory effect of a given compound on autoimmune disease, we screened many compounds with an in vitro Th differentiation assay. BJ-3105, a 6-alkoxypyridin-3-ol analog, inhibited IFN-γ and IL-17 production from polyclonal CD4+ T cells and ovalbumin (OVA)-specific CD4+ T cells which were activated by T cell receptor (TCR) engagement...
2017: PloS One
https://www.readbyqxmd.com/read/28094319/helminth-induced-ly6c-hi-monocyte-derived-alternatively-activated-macrophages-suppress-experimental-autoimmune-encephalomyelitis
#17
Cesar Terrazas, Juan de Dios Ruiz-Rosado, Stephanie A Amici, Kyle A Jablonski, Diana Martinez-Saucedo, Lindsay M Webb, Hanna Cortado, Frank Robledo-Avila, Steve Oghumu, Abhay R Satoskar, Miriam Rodriguez-Sosa, Luis I Terrazas, Mireia Guerau-de-Arellano, Santiago Partida-Sánchez
Helminths cause chronic infections and affect the immune response to unrelated inflammatory diseases. Although helminths have been used therapeutically to ameliorate inflammatory conditions, their anti-inflammatory properties are poorly understood. Alternatively activated macrophages (AAMϕs) have been suggested as the anti-inflammatory effector cells during helminth infections. Here, we define the origin of AAMϕs during infection with Taenia crassiceps, and their disease-modulating activity on the Experimental Autoimmune Encephalomyelitis (EAE)...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094101/retinoic-acid-and-immune-homeostasis-a-balancing-act
#18
REVIEW
Martje N Erkelens, Reina E Mebius
In the immune system, the vitamin A metabolite retinoic acid (RA) is known for its role in inducing gut-homing molecules in T and B cells, inducing regulatory T cells (Tregs), and promoting tolerance. However, it was suggested that RA can have a broad spectrum of effector functions depending on the local microenvironment. Under specific conditions, RA can also promote an inflammatory environment. We discuss the dual role of RA in immune responses and how this might be regulated. Furthermore, we focus on the role of RA in autoimmune diseases and whether RA might be used as a therapeutic agent...
January 13, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28094061/vitiligo-like-lesions-occurring-in-patients-receiving-anti-programmed-cell-death-1-therapies-are-clinically-and-biologically-distinct-from-vitiligo
#19
Maiana Larsabal, Aurélie Marti, Clément Jacquemin, Jérôme Rambert, Denis Thiolat, Léa Dousset, Alain Taieb, Caroline Dutriaux, Sorilla Prey, Katia Boniface, Julien Seneschal
BACKGROUND: The use of anti-programmed cell death (PD)-1 therapies in metastatic tumors is associated with cutaneous side effects including vitiligo-like lesions. OBJECTIVE: We sought to characterize clinically and biologically vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies by studying a case series of 8 patients with metastatic tumors and 30 control subjects with vitiligo. METHODS: Eight patients receiving anti-PD-1 therapies with features of vitiligo-like lesions seen in our department were recruited...
January 13, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28093526/cathepsin-k-deficiency-ameliorates-systemic-lupus-erythematosus-like-manifestations-in-faslpr-mice
#20
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Vasileios C Kyttaris, Isaac E Stillman, Bruce Gelb, Peter Libby, George C Tsokos, Guo-Ping Shi
Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but is also inducible under inflammatory conditions. Fas(lpr) mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus-like manifestations. Although normal mouse kidneys expressed negligible CatK, those from Fas(lpr) mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Fas(lpr) mice also showed elevated serum CatK levels. CatK deficiency in Fas(lpr) mice reduced all tested kidney pathologies, including glomerulus and tubulointerstitial scores, glomerulus complement C3 and IgG deposition, chemokine expression and macrophage infiltration, and serum autoantibodies...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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