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SLE AND T cells

Ji Yang, Xue Yang, Jie Yang, Ming Li
OBJECTIVE: Hydroxychloroquine (HCQ) is a commonly used medicine for the treatment of systemic lupus erythematosus (SLE), and Th17 cells are closely related to the pathogenesis of SLE. However, the role and mechanism of HCQ on Th17 cell differentiation in SLE is not clearly understood. Here, we investigate the effect of HCQ on Th17 cell differentiation both in vitro and in patients with SLE. METHODS: Twenty-five patients with SLE were divided into 2 treatment groups: prednisone alone and HCQ plus prednisone...
March 15, 2018: Journal of Rheumatology
Alicja Kalinowska-Łyszczarz, Mikołaj A Pawlak, Aleksandra Wyciszkiewicz, Katarzyna Pawlak-Buś, Piotr Leszczyński, Mariusz Puszczewicz, Włodzimierz Paprzycki, Wojciech Kozubski, Sławomir Michalak
OBJECTIVE: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains poorly understood. Damage within the CNS is driven by the autoimmune response; however, immunopathophysiology of neuropsychiatric (NP) SLE is multifactorial. Immune cell neurotrophin production could be neuroprotective against autoimmunity-driven CNS damage, as has been shown in multiple sclerosis. The aim of this study was to establish whether immune cell neurotrophin production is associated with damage severity in NPSLE...
March 14, 2018: Neuroimmunomodulation
Gabriela Recalde, Tamara Moreno-Sosa, Florencia Yudica, Cristian A Quintero, Belén Sanchez, Graciela A Jahn, Alexis M Kalergis, Juan Pablo Mackern-Oberti
In this review we discuss how sex steroids and prolactin affect regulation and responsiveness of B and T cells. Sex hormones exert profound effects on several physiological processes of non- reproductive tissues. In the immune system, several studies with experimental models for SLE have shown a noticeable pro-inflammatory role for ERα, contributing to disease development reflected in proteinuria and renal pathology. On the other hand, ERβ appears to have an anti- inflammatory and immunosuppressive effect...
March 8, 2018: Autoimmunity Reviews
Laurence E Cheng, Zahir Amoura, Benjamin Cheah, Falk Hiepe, Barbara A Sullivan, Lei Zhou, Gregory E Arnold, Wayne H Tsuji, Joan T Merrill, James B Chung
OBJECTIVE: Evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T-cell costimulator ligand (ICOSL), in patients with systemic lupus erythematosus (SLE) with arthritis. METHODS: In this phase 1b, randomized, double-blind, placebo-controlled study, patients received AMG 557 210 mg (n=10) or placebo (n=10) weekly for 3 weeks, then every other week for 10 additional doses. Corticosteroids were tapered to ≤7...
March 7, 2018: Arthritis & Rheumatology
Peng Zhang, Qianjin Lu
Immunological tolerance loss is fundamental to the development of autoimmunity; however, the underlying mechanisms remain elusive. Immune tolerance consists of central and peripheral tolerance. Central tolerance, which occurs in the thymus for T cells and bone marrow for B cells, is the primary way that the immune system discriminates self from non-self. Peripheral tolerance, which occurs in tissues and lymph nodes after lymphocyte maturation, controls self-reactive immune cells and prevents over-reactive immune responses to various environment factors...
March 5, 2018: Cellular & Molecular Immunology
Anette Holck Draborg, Niclas Stefan Rasmussen, Janni Lisander Larsen, Charlotte Sværke Jørgensen, Noreen Sandhu, Kristin Skogstrand, Søren Jacobsen, Gunnar Houen
We investigated immune responses to a lytic cytomegalovirus antigen (CMVpp52), and to a lytic human herpes virus (HHV) 6 antigen (HHV6p41), in systemic lupus erythematosus (SLE) patients and healthy controls (HCs), in order to clarify if the previously established impaired responses to Epstein-Barr virus (EBV) in SLE patients is a general defect in their responses against (all) HHVs. Multiplex Luminex technology results showed a normal induction of five quantified cytokines (interferon γ, interleukin(IL)12, IL17, IL10, and tumor necrosis factor α) in SLE patients compared to HCs upon stimulation with CMVpp52 and HHV6p41...
2018: PloS One
R J Zhang, X Zhang, J Chen, M Shao, Y Yang, B Balaubramaniam, X L Sun, J L Ambrus, J He, Z G Li
Objective Serum soluble CD25 (sCD25) could be used as a biomarker for disease activity in conditions associated with T-cell activation including various autoimmune diseases. This study aimed to explore the role of sCD25 as an indicator of disease activity and organ involvement in patients with systemic lupus erythematosus (SLE). Methods Serum samples were collected from 107 SLE patients and 92 age-matched healthy controls (HCs). All patients were followed up for 24 weeks, and sCD25 was measured by enzyme-linked immunosorbent assay...
January 1, 2018: Lupus
Sonia Zeggar, Katsue S Watanabe, Sanae Teshigawara, Sumie Hiramatsu, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Toshiro Niki, Mitsuomi Hirashima, Jun Wada
OBJECTIVE: In systemic lupus erythematosus (SLE), an autoimmune disease associated with multiple organ involvements, lupus nephritis determines prognosis and arthritis impairs quality of life of patients. Galectin-9 (Gal-9, Lgals9) is a β-galactoside binding lectin and the attempts for its clinical application have been made in autoimmune diseases, since recombinant Gal-9 as a ligand for Tim-3 induces apoptosis in activated CD4+ Tim-3+ Th1 cell. We investigated wethere the deficiency of Lgals9 is beneficial or deleterious in lupus mice models...
February 26, 2018: Arthritis & Rheumatology
Zhuochun Huang, Qian Niu, Bin Yang, Junlong Zhang, Min Yang, Huan Xu, Bei Cai, Jing Hu, Yongkang Wu, Lanlan Wang
HLA-II molecules are critical in triggering human immune response, especially in activating CD4+ T cells. HLA-DP, belonging to HLA-II molecules, draws increasing attention for its role in presentation of viral antigen and autoantigen to T cells. Researches reported single nucleotide polymorphism (SNP) of HLA-DP associated with HBV infection and autoimmune diseases such as SLE. However, little is known about the relationship between HLA-DP and rheumatoid arthritis (RA). Rs9277535 is located in 3' UTR region of HLA-DPB1, a subunit of HLA-DP, and was reported to affect HLA-DP mRNA expression...
February 23, 2018: Clinical Rheumatology
Niklas Hagberg, Martin Joelsson, Dag Leonard, Sarah Reid, Maija-Leena Eloranta, John Mo, Magnus K Nilsson, Ann-Christine Syvänen, Yenan T Bryceson, Lars Rönnblom
OBJECTIVES: Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ+ cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2...
February 23, 2018: Annals of the Rheumatic Diseases
Antonio La Cava
PURPOSE OF REVIEW: There has been great interest in understanding why T regulatory cells (Tregs) are reduced in number and/or in function in several autoimmune diseases including systemic lupus erythematosus (SLE). Although research has provided some answers, there is still much to learn. RECENT FINDINGS: Recent investigations on the mechanisms responsible for the impairment of the Tregs in SLE have identified relevant abnormalities in cellular and molecular pathways that have been instrumental in the design of studies in animal models and in the development of pilot immunotherapeutic studies in lupus patients...
February 21, 2018: Current Rheumatology Reports
Cuili Huang, Lidan Zhang, Fang Ling, Sijian Wen, Yanyan Luo, Hui Liu, Jingping Liu, Wenjun Zheng, Ming Liang, Jian Sun, You-Kun Lin
Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease in which tissue damage is caused by autoantibodies. The induction of specific immune tolerance, including the utilization of immune regulatory cells, may enhance the therapeutic effects of organ transplantation in patients with SLE. Furthermore, inhibiting immune responses has been reported to be an effective treatment for SLE. However, few studies have explored the association between an increased immune tolerance and a decreased immune response in SLE treatment...
March 2018: Experimental and Therapeutic Medicine
K E Cervantes-Luevano, N Caronni, M C Castiello, E Fontana, G Piperno, A Naseem, P Uva, M Bosticardo, G E Marcovecchio, L D Notarangelo, M P Cicalese, A Aiuti, A Villa, F Benvenuti
BACKGROUND: Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency caused by mutations in WASp, a key regulator of cytoskeletal dynamics in hematopoietic cells. A high proportion of patients develop autoimmunity due to a breakdown in T and B cell tolerance. Moreover, excessive production of type-I interferon by plasmacytoid DCs contribute to autoimmune signs, however, the factors that triggers excessive innate activation have not been defined. OBJECTIVE: Neutrophils extracellular traps (NETs) emerged as major initiating factors in diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)...
February 12, 2018: Journal of Allergy and Clinical Immunology
Wei Liang, Shanshan Mao, Shijie Sun, Ming Li, Zhi Li, Rui Yu, Tonghui Ma, Jianguo Gu, Jianing Zhang, Naoyuki Taniguchi, Wenzhe Li
CD4+ T cell activation promotes the pathogenic process of systemic lupus erythematosus (SLE). T cell receptor (TCR) complex are highly core fucosylated glycoproteins, which play important roles in T cell activation. In this study, we found that the core fucosylation of CD4+ T cells was significantly increased in SLE patients. Loss of core fucosyltransferase (Fut8), the sole enzyme for catalyzing the core fucosylation of N-glycan, significantly reduced CD4+ T cell activation and ameliorated the experimental autoimmune encephalomyelitis-induced syndrome in Fut8-/- mice...
2018: Frontiers in Immunology
D Brandt, C M Hedrich
TCRαβ+CD3+CD4-CD8-"double negative" (DN) T cells comprise a small subset of mature peripheral T cells. The origin and function of DN T cells are somewhat unclear and discussed controversially. While DN T cells resemble a rare and heterogeneous T cell subpopulation in healthy individuals, numbers of TCRαβ+DN T cells are expanded in several inflammatory conditions, where they also exhibit distinct effector phenotypes and infiltrate inflamed tissues. Thus, DN T cells may be involved in systemic inflammation and tissue damage in autoimmune/inflammatory conditions, including SLE, Sjögren's syndrome, and psoriasis...
February 8, 2018: Autoimmunity Reviews
Zhen Zhao, Xiaojuan Zhang, Lili Su, Le Xu, Yong Zheng, Jian Sun
Although Interleukin-2 (IL-2) was identified almost 40 years ago, only recently low dosage IL-2 therapy is proved to be an effective approach to treat autoimmune diseases. The underlining mechanism is that IL-2 can fine-tune subsets of CD4+ T cells by promoting the development and maintenance of regulatory T cells (Treg) at low-dosage (ld) and enhance the functions of effector T cells (Teff) at high-dosage (hd). Since the successful clinical trials of IL-2 to treat patients with autoimmune diseases and inflammatory conditions, including Systemic lupus erythematosus (SLE) and Type 1 Diabetes (T1D), ld IL-2 therapy is a promising strategy to treat autoimmune diseases...
January 31, 2018: International Immunopharmacology
Chen Liu, Dongwei Wang, Ying Song, Songsong Lu, Jingzhong Zhao, Hui Wang
As one specialized subset of regulatory T cells (Tregs), follicular regulatory T cells (TFR) could suppress follicular helper T cells (TFH) and B cells in germinal centers to maintain immune homeostasis. The unbalance of TFR and TFH cells could result in abnormal germinal center responses and contribute to pathogenesis of autoimmune diseases. However, the role of TFR cells in systemic lupus erythematosus (SLE) remains unclear. This study revealed a significant increase of CD4+CXCR5+FOXP3+ TFR cells in peripheral blood of SLE patients compared with healthy controls...
January 30, 2018: International Immunopharmacology
Katerina Bakela, Myrsini Dimakopoulou, Panagiota Batsou, Nikos Manidakis, Irene Athanassakis
Taking into consideration the multiparametric nature of systemic lupus erythematosus (SLE), the severity and variability of symptoms and the lack of effective therapeutic approaches, the present study took advantage of the recently described role of soluble major histocompatibility complex class II (sMHCII) molecules in maintaining tolerance to the organism and attempted to apply sMHCII proteins as a treatment to murine SLE experimental models in vitro as well as in vivo. After breaking tolerance to DNA in vitro, which was accompanied by development of specific anti-dsDNA antibodies, syngeneic or allogeneic sMHCII molecules, purified from healthy mouse serum, could significantly reduce the specific antibody levels and drive the system towards immunosuppression, as assessed by specific marker analysis on T cells and cytokine production by flow cytometry and ELISA respectively...
February 7, 2018: Scandinavian Journal of Immunology
Jae-Seung Moon, Chin Hee Mun, Jung-Ho Kim, Jen-Young Cho, Sung-Dong Park, Tae-Yoon Park, Jin-Su Shin, Chun-Chang Ho, Yong-Beom Park, Sankar Ghosh, Alfred L M Bothwell, Sang-Won Lee, Sang-Kyou Lee
Excessive expression of Tbet and IFNγ is evidence of systemic lupus erythematosus (SLE) in lupus patients. In this study, the nucleus-transducible form of Transcription Modulation Domain (TMD) of Tbet (ntTbet-TMD), which is a fusion protein between Protein Transduction Domain Hph-1 (Hph-1-PTD) and the TMD of Tbet comprising DNA binding domain and isotype-specific domain, was generated to inhibit Tbet-mediated transcription in the interactomic manner. ntTbet-TMD was effectively delivered into the nucleus of the cells and specifically inhibited Tbet-mediated transcription without influencing the differentiation of other T cell subsets and signaling events for T cell activation...
February 3, 2018: Kidney International
Maria Wigren, Elisabet Svenugnsson, Ingrid Yao Mattisson, Johanna T Gustafsson, Iva Gunnarsson, Agneta Zickert, Kerstin Elvin, Kerstin Jensen-Urstad, Anders Bengtsson, Birgitta Gullstrand, Gunilla Nordin Fredrikson, Jan Nilsson
BACKGROUND AND AIMS: There is convincing evidence that adaptive immune responses affect the development of atherosclerosis and thrombosis and several autoimmune diseases are associated with increased cardiovascular risk. However, our understanding of the underlying mechanisms remains limited. We investigated how biomarkers reflecting four aspects of autoimmunity: apoptosis, inflammation, tissue degradation and repair, associate with cardiovascular disease (CVD) in subjects with systemic lupus erythematosus (SLE)...
March 2018: Atherosclerosis
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