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A C Lozada-Navarro, D Castillo-Martínez, M Moreno-Ramírez, G Acosta-Peña, A Páez, F Massó, R Márquez-Velasco, L M Amezcua-Guerra
Objective The objective was to assess the proportion of Th1, Th2 and Th17 phenotypes in senescent CD4+ CD28null cells from patients with systemic lupus erythematosus (SLE) and its association with the pattern of joint involvement. Methods This cross-sectional study was performed in SLE patients with erosive arthritis (rhupus) or nondeforming, nonerosive arthritis. Total CD4+ CD28null cells as well as the proportion of these cells expressing T-bet, GATA3 or RORγt were analyzed by color-flow cytometry. Serum osteopontin levels were measured by ELISA...
August 15, 2018: Lupus
Dirk Baumjohann, Vigo Heissmeyer
T follicular helper (Tfh) cells are critically involved in the establishment of potent antibody responses against infectious pathogens, such as viruses and bacteria, but their dysregulation may also result in aberrant antibody responses that frequently coincide with autoimmune diseases or allergies. The fate and identity of Tfh cells is tightly controlled by gene regulation on the transcriptional and posttranscriptional level. Here, we provide deeper insights into the posttranscriptional mechanisms that regulate Tfh cell differentiation, function, and plasticity through the actions of RNA-binding proteins (RBPs) and small endogenously expressed regulatory RNAs called microRNAs (miRNAs)...
2018: Frontiers in Immunology
Rajesh Mani, Manish Gupta, Anshu Malik, Ravi Tandon, Rajendra Prasad, Rakesh Bhatnagar, Nirupama Banerjee
Novel adjuvants are in demand for improving the efficacy of human vaccines. The immunomodulatory properties of Mycobacterium tuberculosis (Mtb) cell wall components have been highlighted in the formulation of complete Freund's adjuvant (CFA). We have explored the adjuvant potential of poly-α-L-glutamine (PLG), a lesser-known constituent of pathogenic mycobacterial cell wall. Immune parameters indicated that the adjuvant potency of PLG was statistically comparable to CFA and better than alum in the context of H1 antigen (Ag85B and ESAT-6 fusion)...
August 13, 2018: Infection and Immunity
Anyan Xie, René J Robles, Samiran Mukherjee, Haohai Zhang, Linda Feldbrügge, Eva Csizmadia, Yan Wu, Keiichi Enjyoji, Alan C Moss, Leo E Otterbein, Francisco J Quintana, Simon C Robson, Maria Serena Longhi
In Crohn's disease, pathogenic Th17-cells express low levels of CD39 ectonucleotidase and are refractory to the immunosuppressive effects of unconjugated bilirubin (UCB), an endogenous ligand for aryl-hydrocarbon-receptor (AhR). This resistance to AhR ligation might be associated with alterations in responses to hypoxia. Limited exposure to hypoxia appears beneficial in acute tissue injury. However, in protracted inflammation, hypoxemia may paradoxically result in Th17-cell activation. We report here that in vitro exposure of Th17-cells from Crohn's disease patients to hypoxia limits responsiveness to AhR stimulation by UCB, as reflected by lower CD39 levels...
August 8, 2018: Journal of Autoimmunity
Seagal Teitz-Tennenbaum, Steven P Viglianti, Jonathan A Roussey, Stuart M Levitz, Michal A Olszewski, John J Osterholzer
The substantial morbidity and mortality caused by invasive fungal pathogens, including Cryptococcus neoformans , necessitates increased understanding of protective immune responses against these infections. Our previous work using murine models of cryptococcal lung infection demonstrated that dendritic cells (DCs) orchestrate critical transitions from innate to adaptive immunity and that IL-10 signaling blockade improves fungal clearance. To further understand interrelationships among IL-10 production, fungal clearance, and the effect of IL-10 on lung DCs, we performed a comparative temporal analysis of cryptococcal lung infection in wild type C57BL/6J mice (designated IL-10+/+ ) and IL-10-/- mice inoculated intratracheally with C...
August 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Amédée Renand, Sarah Habes, Jean-François Mosnier, Hélène Aublé, Jean-Paul Judor, Nicolas Vince, Philippe Hulin, Steven Nedellec, Sylvie Métairie, Isabelle Archambeaud, Sophie Brouard, Jérôme Gournay, Sophie Conchon
Autoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from the peripheral blood of new-onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11), and healthy subjects (n = 14). Liver biopsy analyses were performed to complete the blood phenotypic analysis...
August 2018: Hepatology Communications
Yuli Cheng, Xing Zhu, Xiaohuan Wang, Qinghui Zhuang, Xu Huyan, Ximeng Sun, Jingjing Huang, Bin Zhan, Xinping Zhu
Helminth infection induces Th2-biased immune responses and inhibitory/regulatory pathways that minimize excessive inflammation to facilitate the chronic infection of helminth in the host and in the meantime, prevent host hypersensitivity from autoimmune or atopic diseases. However, the detailed molecular mechanisms behind modulation on inflammatory diseases are yet to be clarified. Programmed death 1 (PD-1) is one of the important inhibitory receptors involved in the balance of host immune responses during chronic infection...
2018: Frontiers in Immunology
Aakanksha Jain, Ran Song, Edward K Wakeland, Chandrashekhar Pasare
Innate cytokines are critical drivers of priming and differentiation of naive CD4 T cells, but their functions in memory T cell response are largely undefined. Here we show that IL-1 acts as a licensing signal to permit effector cytokine production by pre-committed Th1 (IFN-γ), Th2 (IL-13, IL-4, and IL-5) and Th17 (IL-17A, IL-17F, and IL-22) lineage cells. This licensing function of IL-1 is conserved across effector CD4 T cells generated by diverse immunological insults. IL-1R signaling stabilizes cytokine transcripts to enable productive and rapid effector functions...
August 9, 2018: Nature Communications
Krystin Deason, Ty Dale Troutman, Aakanksha Jain, Dilip K Challa, Rajakumar Mandraju, Travis Brewer, E Sally Ward, Chandrashekhar Pasare
The toll-like receptor (TLR) and interleukin (IL)-1 family of receptors share several signaling components, including the most upstream adapter, MyD88. We previously reported the discovery of B cell adapter for phosphoinositide 3-kinase (BCAP) as a novel toll-IL-1 receptor homology domain-containing adapter that regulates inflammatory responses downstream of TLR signaling. Here we find that BCAP plays a critical role downstream of both IL-1 and IL-18 receptors to regulate T helper (Th) 17 and Th1 cell differentiation, respectively...
August 9, 2018: Journal of Experimental Medicine
Sarah K Whitley, Anand Balasubramani, Carlene Zindl, Ranjan Sen, Yoichiro Shibata, Gregory E Crawford, Nathaniel M Weathington, Robin D Hatton, Casey T Weaver
IL-1β plays a critical role in IL-6- and TGFβ- initiated Th17 differentiation and induction of Th17-mediated autoimmunity. However, the means by which IL-1 regulates various aspects of Th17 development remains poorly understood. We recently reported that IL-1β enhances STAT3 phosphorylation via NF-kB-mediated repression of SOCS3 to facilitate Il17 transcription and Th17 differentiation, identifying an effect of IL-1 signaling on proximal events of STAT3 signaling. Here we show that IL-1β promotes STAT3 binding to key cis-elements that control IL-17 expression...
August 9, 2018: Journal of Biological Chemistry
Matthew Cummings, Anitha Christy Sigamani Arumanayagam, Picheng Zhao, Sunil Kannanganat, Olaf Stuve, Nitin J Karandikar, Todd N Eagar
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) where pathology is thought to be regulated by autoreactive T cells of the Th1 and Th17 phenotype. In this study we sought to understand the functions of Presenilin 1 (PSEN1) in regulating T cell effector responses in the experimental autoimmune encephalomyelitis (EAE) murine model of MS. PSEN1 is the catalytic subunit of γ-secretase a multimolecular protease that mediates intramembranous proteolysis. γ-secretase is known to regulate several pathways of immune importance...
2018: PloS One
Yanxia Lu, Hassen Kared, Shu Wen Tan, Etienne Becht, Evan W Newell, Hugo P S Van Bever, Tze Pin Ng, Anis Larbi
Asthma comprises heterogeneous clinical subtypes driven by diverse pathophysiological mechanisms. We characterized the modulation of the inflammatory environment with the phenotype, gene expression, and function of helper CD4 T cells among acutely exacerbated and stable asthma patients. Systemic Th2 immune deviation (IgE and Th2 cytokines) and inflammation (IL-6, CRP) were associated with increased Th17 cells during acute asthma. Th2/Th17 cell differentiation during acute asthma was regulated by the enhanced expression of transcription factors (c-MAF, IRF-4)...
August 7, 2018: Mucosal Immunology
Fernanda Garcia Spina, Aída Gouvea, Regina Célia de Menezes Succi, Flavia Calanca, Lily Yin Weckx, Maria Teresa Terreri, Maria Aparecida Sakauchi Takano, Maria Isabel de Moraes-Pinto
BACKGROUND: Pertussis cases have increased worldwide and knowledge on immune response and cytokine profile after Tdap vaccine in immunodeficient adolescents is scarce. OBJECTIVE: To evaluate the immune response after Tdap in HIV-infected (HIV) and in healthy adolescents (CONTROL). METHODOLOGY: Thirty HIV adolescents with CD4 cell counts >200 and 30 CONTROLs were immunized with Tdap, after a prior whole-cell DTP vaccine primary scheme...
August 4, 2018: Vaccine
Bogdan Jakiela, Joanna Kosałka, Hanna Plutecka, Stanisława Bazan-Socha, Marek Sanak, Jacek Musial
The objective of this study was to investigate the mechanisms of Th17 expansion in lupus nephritis (LN) patients, and determine whether it is associated with impaired function of regulatory T-cells (Treg). Major effector subsets of peripheral blood CD4+ T-cells were assessed by flow cytometry in 33 LN patients with different activity of the disease, and 19 healthy controls. Percentage of circulating Th17 cells was increased in LN (median 1.2% of CD4+ as compared to 0.6% in control group, P<0.01), while Treg cells remained unchanged (12...
August 7, 2018: Clinical and Experimental Immunology
Xiaojun Lin, Qiuyi Sun, Ling Zhou, Minhong He, Xiaoying Dong, Mingqiang Lai, Miao Liu, Yongchun Su, Chunhong Jia, Zelong Han, Side Liu, Hang Zheng, Yu Jiang, Hui Ling, Mangmang Li, Juan Chen, Zhipeng Zou, Xiaochun Bai
The functional role of colonic epithelium in the pathogenesis of ulcerative colitis (UC) remains unclear. Here, we reveal a novel mechanism by which colonic epithelia recruit T helper-17 (Th17) cells during the onset of UC. mTOR complex 1 (mTORC1) was hyper-activated in colonic epithelia of UC mice. While colonic epithelial TSC1 (mTORC1 negative regulator) disruption induced constitutive mTORC1 activation in the colon epithelia and aggravated UC, RPTOR (essential mTORC1 component) depletion inactivated mTORC1 and ameliorated UC...
August 6, 2018: Mucosal Immunology
Jong Y Lee, Geum J Kim, Jin K Choi, Young-Ae Choi, Na-Hee Jeong, Pil-Hoon Park, Hyukjae Choi, Sang-Hyun Kim
Rheumatoid arthritis (RA) is a progressive autoimmune disease specific to synovial joints; it causes joint damage and other systemic abnormalities, thereby leading to physical disability and early mortality. Marine sponge-derived fungi, Pestalotiopsis sp., secrete immunosuppressive compounds in the culture broth. In the present study, we isolated 4-(hydroxymethyl)catechol (4-HMC) from these fungal species, and evaluated its anti-RA effects using a murine collagen-induced arthritis model and tumor necrosis factor-α-stimulated human RA synovial fibroblasts...
2018: Frontiers in Pharmacology
Chen Liu, Juntao Chen, Baoqing Liu, Shunzong Yuan, Dawei Shou, Liang Wen, Xiaoying Wu, Weihua Gong
Since pro-inflammatory cytokine IL-18 and its receptor (IL-18R) are closely involved in regulating both adaptive and innate immune responses, it is conceivable that they might play an important role in organ transplantation. IL-18 can stimulate lymphocytes to produce the IFN-γ and regulate macrophage activity, thereby increasing the expression of proinflammatory cytokines including IL-1β, IL-6, CCL4 (macrophage inflammatory protein-1 β), CXCL2 (macrophage inflammatory protein-2), and CCL2 (monocyte chemotactic protein-1)...
August 3, 2018: European Cytokine Network
Qian-Lan Zhou, Tian-Yue Wang, Miao Li, Yun-Xiao Shang
Allergic asthma is a chronic inflammatory disease of the airways. T lymphocytes play an important role in the pathogenesis of asthma. The voltage-gated Kv1.3 potassium channel is a target for the preferential inhibition of TEM cells. In this study, we investigate the effects of PAP-1, a selective inhibitor of Kv1.3 channel, on the treatment of the neutrophilic asthma model. PAP-1 (40 mg/kg) was injected intraperitoneally into ovalbumin (OVA)-lipopolysaccharide (LPS)-challenged BALB/c mice. We found that the expression of the Kv1...
August 2, 2018: International Immunopharmacology
Kyoko Yamaguchi, Koji Mishima, Hirofumi Ohmura, Fumiyasu Hanamura, Mamoru Ito, Michitaka Nakano, Kenji Tsuchihashi, Shun-Ichiro Ota, Naoko Wada, Hiroshi Uchi, Hiroshi Ariyama, Hitoshi Kusaba, Hiroaki Niiro, Koichi Akashi, Eishi Baba
Human anti-programmed death-1 (PD-1) antibody possesses the capability to revitalize host T cells and has been an effective therapy for metastatic malignant melanoma (MM). However, the precise subsets of T cells predominantly activated by anti-PD-1 have not yet been clarified. In this study, peripheral blood mononuclear cells obtained from MM patients scheduled to receive anti-PD-1 (nivolumab) therapy, and healthy subjects (HS), were systematically examined by flow cytometry to identify changes in the proportion of immune cell subsets...
August 1, 2018: Cancer Science
Biswajit Das, Curtis Dobrowolski, Benjamin Luttge, Saba Valadkhan, Nicolas Chomont, Rowena Johnston, Peter Bacchetti, Rebecca Hoh, Monica Gandhi, Steven G Deeks, Eileen Scully, Jonathan Karn
Unbiased shRNA library screens revealed that the estrogen receptor-1 (ESR-1) is a key factor regulating HIV-1 latency. In both Jurkat T cells and a Th17 primary cell model for HIV-1 latency, selective estrogen receptor modulators (SERMs, i.e., fulvestrant, raloxifene, and tamoxifen) are weak proviral activators and sensitize cells to latency-reversing agents (LRAs) including low doses of TNF-α (an NF-κB inducer), the histone deacetylase inhibitor vorinostat (soruberoylanilide hydroxamic acid, SAHA), and IL-15...
July 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
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