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https://www.readbyqxmd.com/read/27902985/disease-manifestation-and-inflammatory-activity-as-modulators-of-th17-treg-balance-and-rorc-foxp3-methylation-in-systemic-sclerosis
#1
Giovanni Almanzar, Matthias Klein, Marc Schmalzing, Deborah Hilligardt, Nady El Hajj, Hermann Kneitz, Vanessa Wild, Andreas Rosenwald, Sandrine Benoit, Henning Hamm, Hans-Peter Tony, Thomas Haaf, Matthias Goebeler, Martina Prelog
BACKGROUND: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. METHODS: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors...
December 1, 2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27895171/impairment-of-ccr6-and-cxcr3-th-cell-migration-in-hiv-1-infection-is-rescued-by-modulating-actin-polymerization
#2
Valentina Cecchinato, Enos Bernasconi, Roberto F Speck, Michele Proietti, Ulrike Sauermann, Gianluca D'Agostino, Gabriela Danelon, Tanja Rezzonico Jost, Fabio Grassi, Lorenzo Raeli, Franziska Schöni-Affolter, Christiane Stahl-Hennig, Mariagrazia Uguccioni
CD4(+) T cell repopulation of the gut is rarely achieved in HIV-1-infected individuals who are receiving clinically effective antiretroviral therapy. Alterations in the integrity of the mucosal barrier have been indicated as a cause for chronic immune activation and disease progression. In this study, we present evidence that persistent immune activation causes impairment of lymphocytes to respond to chemotactic stimuli, thus preventing their trafficking from the blood stream to peripheral organs. CCR6(+) and CXCR3(+) Th cells accumulate in the blood of aviremic HIV-1-infected patients on long-term antiretroviral therapy, and their frequency in the circulation positively correlates to levels of soluble CD14 in plasma, a marker of chronic immune activation...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27870827/augmented-th17-type-immune-responses-in-preterm-neonates-exposed-to-histologic-chorioamnionitis
#3
Daniel C Rito, Luke T Viehl, Paula M Buchanan, Seema Haridas, Joyce M Koenig
BACKGROUND: Histologic chorioamnionitis (HCA) is a placental inflammatory disorder that frequently precedes preterm delivery. HCA increases risk for long-standing inflammatory injury and may influence immune programming, particularly in preterm (PT) neonates. We hypothesized that HCA exposure is associated with an increased circulating frequency of pro-inflammatory, Th17-type responses. METHODS: Placental cord blood was collected from HCA-exposed or control neonates (23-41 weeks gestation)...
November 21, 2016: Pediatric Research
https://www.readbyqxmd.com/read/27851911/autoimmune-renal-disease-is-exacerbated-by-s1p-receptor-1-dependent-intestinal-th17-cell-migration-to-the-kidney
#4
Christian F Krebs, Hans-Joachim Paust, Sonja Krohn, Tobias Koyro, Silke R Brix, Jan-Hendrik Riedel, Patricia Bartsch, Thorsten Wiech, Catherine Meyer-Schwesinger, Jiabin Huang, Nicole Fischer, Philipp Busch, Hans-Willi Mittrücker, Ulrich Steinhoff, Brigitta Stockinger, Laura Garcia Perez, Ulrich O Wenzel, Matthias Janneck, Oliver M Steinmetz, Nicola Gagliani, Rolf A K Stahl, Samuel Huber, Jan-Eric Turner, Ulf Panzer
Th17 cells are most abundant in the gut, where their presence depends on the intestinal microbiota. Here, we examined whether intestinal Th17 cells contribute to extra-intestinal Th17 responses in autoimmune kidney disease. We found high frequencies of Th17 cells in the kidneys of patients with antineutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis. We utilized photoconversion of intestinal cells in Kaede mice to track intestinal T cell mobilization upon glomerulonephritis induction, and we found that Th17 cells egress from the gut in a S1P-receptor-1-dependent fashion and subsequently migrate to the kidney via the CCL20/CCR6 axis...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27835617/hiv-persists-in-ccr6-cd4-t-cells-from-colon-and-blood-during-antiretroviral-therapy
#5
Annie Gosselin, Tomas Raul Wiche Salinas, Delphine Planas, Vanessa S Wacleche, Yuwei Zhang, Rémi Fromentin, Nicolas Chomont, Éric A Cohen, Barbara Shacklett, Vikram Mehraj, Maged P Ghali, Jean-Pierre Routy, Petronela Ancuta
OBJECTIVES: The objective of this article is to investigate the contribution of colon and blood CD4 T-cell subsets expressing the chemokine receptor CCR6 to HIV persistence during antiretroviral therapy. DESIGN: Matched sigmoid biopsies and blood samples (n = 13) as well as leukapheresis (n = 20) were collected from chronically HIV-infected individuals receiving antiretroviral therapy. Subsets of CD4 T cells with distinct differentiation/polarization profiles were identified using surface markers as follows: memory (TM, CD45RA), central memory (TCM; CD45RACCR7), effector (TEM/TM; CD45RACCR7), Th17 (CCR6CCR4), Th1Th17 (CCR6CXCR3), Th1 (CCR6CXCR3), and Th2 (CCR6CCR4)...
January 2, 2017: AIDS
https://www.readbyqxmd.com/read/27822475/rank-expression-and-osteoclastogenesis-in-human-monocytes-in-peripheral-blood-from-rheumatoid-arthritis-patients
#6
Yuki Nanke, Tsuyoshi Kobashigawa, Toru Yago, Manabu Kawamoto, Hisashi Yamanaka, Shigeru Kotake
Rheumatoid arthritis (RA) appears as inflammation of synovial tissue and joint destruction. Receptor activator of NF-κB (RANK) is a member of the TNF receptor superfamily and a receptor for the RANK ligand (RANKL). In this study, we examined the expression of RANK(high) and CCR6 on CD14(+) monocytes from patients with RA and healthy volunteers. Peripheral blood samples were obtained from both the RA patients and the healthy volunteers. Osteoclastogenesis from monocytes was induced by RANKL and M-CSF in vitro...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27800533/natalizumab-treatment-leads-to-an-increase-in-circulating-cxcr3-expressing-b-cells
#7
Maija Saraste, Tarja-Leena Penttilä, Laura Airas
OBJECTIVE: To study the effects of natalizumab treatment on subgroups of circulating peripheral blood B cell populations. METHODS: We studied the proportions and absolute numbers of CD19(+)CD20(+), CD10(+), and CD5(+) B cell populations, and determined very late activation antigen-4 and chemokine receptor CXCR3, CCR5, and CCR6 expression on B cells in the peripheral blood of 14 natalizumab-treated patients with relapsing-remitting multiple sclerosis. Five blood samples per patient were obtained longitudinally before and during the first year of treatment...
December 2016: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/27799287/cd1d-mediated-activation-of-group-3-innate-lymphoid-cells-drives-il-22-production
#8
Julia Saez de Guinoa, Rebeca Jimeno, Nazanin Farhadi, Peter J Jervis, Liam R Cox, Gurdyal S Besra, Patricia Barral
Innate lymphoid cells (ILCs) are a heterogeneous family of immune cells that play a critical role in a variety of immune processes including host defence against infection, wound healing and tissue repair. Whether these cells are involved in lipid-dependent immunity remains unexplored. Here we show that murine ILCs from a variety of tissues express the lipid-presenting molecule CD1d, with group 3 ILCs (ILC3s) showing the highest level of expression. Within the ILC3 family, natural cytotoxicity triggering receptor (NCR)(-)CCR6(+) cells displayed the highest levels of CD1d...
October 31, 2016: EMBO Reports
https://www.readbyqxmd.com/read/27797715/tumor-associated-macrophage-derived-ccl20-enhances-the-growth-and-metastasis-of-pancreatic-cancer
#9
Bingyan Liu, Yiping Jia, Jun Ma, Shaoqiu Wu, Haosheng Jiang, Yan Cao, Xianjun Sun, Xiang Yin, Shuo Yan, Mingyi Shang, Aiwu Mao
Pancreatic cancer is an aggressive malignancy with a high metastatic potential that results in a high mortality rate worldwide. Although macrophages have the potential to kill tumor cells and elicit immune responses against tumors, there is evidence that tumor-associated macrophages (TAMs) promote tumor progression and suppress T-cell responses. CC-chemokine ligand 20 (CCL20) and its unique receptor CC-chemokine receptor 6 (CCR6) are exploited by cancer cells for migration and metastasis and play important roles in the development and progression of cancer...
October 19, 2016: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/27789680/mutation-induced-functional-alterations-of-ccr6
#10
Bina Julian, Kevin Gao, Benjamin N Harwood, Martin Beinborn, Alan S Kopin
The Cys-Cys Chemokine Receptor 6 (CCR6) is a well established modulator of inflammation. Although several genetic associations have been identified between CCR6 polymorphisms and immune system disorders (e.g. rheumatoid arthritis, Crohn's disease), the pharmacological effects of naturally occurring missense mutations in this receptor have yet to be characterized. In this study, we initially assessed G protein-mediated signaling and observed that WT CCR6 exhibited ligand independent activity. In addition we found that the five most frequent CCR6 missense variants (A89T, A150V, R155W, G345S, and A369V) exhibited decreased basal and/or ligand induced Gαi protein signaling...
October 27, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27766171/tissue-specific-induction-of-ccr6-and-nrp1-during-early-cd4-t-cell-differentiation
#11
Joern Pezoldt, Jochen Huehn
Upon differentiation, T cells acquire tissue-specific homing properties allowing efficient targeting of effector T cells into distinct inflamed organs. Priming of T cells within skin-draining, peripheral lymph nodes (pLNs) leads to the expression of E- and P-selectin ligands, which facilitate migration into inflamed skin, whereas activation within gut-draining, mesenteric LNs (mLNs) results in induction of chemokine receptor CCR9 and integrin α4β7, both required for migration of effector T cells into mucosal tissues...
September 29, 2016: European Journal of Microbiology & Immunology
https://www.readbyqxmd.com/read/27758874/replication-of-associations-between-genetic-polymorphisms-and-chronic-graft-versus-host-disease
#12
Paul J Martin, Wenhong Fan, Barry E Storer, David M Levine, Lue Ping Zhao, Edus H Warren, Mary E D Flowers, Stephanie J Lee, Paul A Carpenter, Michael Boeckh, Sangeeta Hingorani, Li Yan, Qiang Hu, Leah Preus, Song Liu, Stephen Spellman, Xiaochun Zhu, Marcelo Pasquini, Philip McCarthy, Daniel Stram, Xin Sheng, Loreall Pooler, Christopher A Haiman, Lara Sucheston-Campbell, Theresa Hahn, John A Hansen
Previous studies have identified single-nucleotide polymorphisms (SNPs) associated with the risk of chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. The current study determined whether these associations could be replicated in large cohorts of donors and recipients. Each SNP was tested with cohorts of patients having the same donor type (HLA-matched related, unrelated, or both) reported in the original publication, and testing was limited to the same genome (recipient or donor) and genetic model (dominant, recessive, or allelic) reported in the original study...
November 17, 2016: Blood
https://www.readbyqxmd.com/read/27755984/mirna-27b-modulates-endothelial-cell-angiogenesis-by-directly-targeting-naa15-in-atherogenesis
#13
Li Qun, Xi Wenda, Sun Weihong, Ma Jianyang, Cai Wei, Lou Fangzhou, Xu Zhenyao, Gao Pingjin
BACKGROUND AND AIMS: The CCL20/CCR6 axis has been shown to play a vital role in the pathogenesis of atherosclerosis (AS). However, the regulatory mechanism remains unclear. Here, we studied the miRNA-mediated epigenetic regulation of the CCL20/CCR6 axis in atherogenesis. METHODS: CCR6(+/+)ApoE-/- and CCR6(-/-)ApoE-/- mice were fed a high-fat diet for 24 weeks. Plaque size was evaluated via ultrasound biomicroscope and hematoxylin and eosin. Protein expression were measured by Western blotting or immunofluorescence/immunohistochemistry or ELISA, and gene mRNA levels were detected by RT-PCR...
October 8, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27753073/mapping-urinary-chemokines-in-human-lupus-nephritis-potentially-redundant-pathways-recruit-cd4-and-cd8-t-cells-and-macrophages
#14
Jan Klocke, Katharina Kopetschke, Anna-Sophie Grießbach, Valerie Langhans, Jens Y Humrich, Robert Biesen, Duska Dragun, Andreas Radbruch, Gerd-Rüdiger Burmester, Gabriela Riemekasten, Philipp Enghard
Renal infiltration of inflammatory cells contributes to the pathogenesis of lupus nephritis (LN). Current knowledge on the recruitment mechanisms relies mainly on findings in rodent models. Here, we assess various chemokine pathways in human LN by comparing urinary chemokine concentrations (in 25 patients with acute LN and in 78 lupus patients without active LN) with the expression of corresponding chemokine receptors on urinary leukocytes (in ten acute LN patients). Nine urinary chemokines were significantly elevated in LN patients and correlated with renal disease activity and urinary cell counts; however, their concentrations displayed considerable interindividual heterogeneity...
October 18, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27751964/altered-expression-of-glial-markers-chemokines-and-opioid-receptors-in-the-spinal-cord-of-type-2-diabetic-monkeys
#15
Norikazu Kiguchi, Huiping Ding, Christopher M Peters, Nancy D Kock, Shiroh Kishioka, J Mark Cline, Janice D Wagner, Mei-Chuan Ko
Neuroinflammation is a pathological condition that underlies diabetes and affects sensory processing. Given the high prevalence of pain in diabetic patients and crosstalk between chemokines and opioids, it is pivotal to know whether neuroinflammation-associated mediators are dysregulated in the central nervous system of diabetic primates. Therefore, the aim of this study was to investigate whether mRNA expression levels of glial markers, chemokines, and opioid receptors are altered in the spinal cord and thalamus of naturally occurring type 2 diabetic monkeys (n=7) compared with age-matched non-diabetic monkeys (n=6)...
October 14, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27711188/immunological-signatures-after-bordetella-pertussis-infection-demonstrate-importance-of-pulmonary-innate-immune-cells
#16
René H M Raeven, Jolanda Brummelman, Larissa van der Maas, Wichard Tilstra, Jeroen L A Pennings, Wanda G H Han, Cécile A C M van Els, Elly van Riet, Gideon F A Kersten, Bernard Metz
Effective immunity against Bordetella pertussis is currently under discussion following the stacking evidence of pertussis resurgence in the vaccinated population. Natural immunity is more effective than vaccine-induced immunity indicating that knowledge on infection-induced responses may contribute to improve vaccination strategies. We applied a systems biology approach comprising microarray, flow cytometry and multiplex immunoassays to unravel the molecular and cellular signatures in unprotected mice and protected mice with infection-induced immunity, around a B...
2016: PloS One
https://www.readbyqxmd.com/read/27699272/effects-of-sphingosine-1-phosphate-receptor-1-phosphorylation-in-response-to-fty720-during-neuroinflammation
#17
Hsing-Chuan Tsai, Yingxiang Huang, Christopher S Garris, Monica A Moreno, Christina W Griffin, May H Han
Fingolimod (FTY720, Gilenya), a sphingosine-1-phosphate receptor (S1PR) modulator, is one of the first-line immunomodulatory therapies for treatment of relapsing-remitting multiple sclerosis (MS). Human S1PR1 variants have been reported to have functional heterogeneity in vitro, suggesting that S1PR1 function may influence FTY720 efficacy. In this study, we examined the influence of S1PR1 phosphorylation on response to FTY720 in neuroinflammation. We found that mice carrying a phosphorylation-defective S1pr1 gene [S1PR1(S5A) mice] were refractory to FTY720 treatment in MOG35-55-immunized and Th17-mediated experimental autoimmune encephalomyelitis (EAE) models...
June 16, 2016: JCI Insight
https://www.readbyqxmd.com/read/27693917/t-cell-clones-from-th1-th17-or-th1-17-lineages-and-their-signature-cytokines-have-different-capacity-to-activate-endothelial-cells-or-synoviocytes
#18
Fabien Lavocat, Laura Maggi, Francesco Annunziato, Pierre Miossec
OBJECTIVE: To compare the direct effect of cytokines on synoviocytes and endothelial cells to the effects of supernatants from Th1, Th17 and Th1/17 clones and the direct cell-cell interactions with the same clones. METHODS: Th17 and Th1/17 clones were obtained from the CD161+CCR6+ fraction and Th1 clones from the CD161-CCR6- fraction of human CD4+ T-cells. Endothelial cells or synoviocytes were cultured in the presence of either isolated pro-inflammatory cytokines (IL-17 and/or TNF-α) or supernatants from the T-cell clones or co-cultured with T-cell clones themselves...
December 2016: Cytokine
https://www.readbyqxmd.com/read/27688600/doxycycline-and-benznidazole-reduce-the-profile-of-th1-th2-and-th17-chemokines-and-chemokine-receptors-in-cardiac-tissue-from-chronic-trypanosoma-cruzi-infected-dogs
#19
Guilherme de Paula Costa, Laís Roquete Lopes, Maria Cláudia da Silva, Aline Luciano Horta, Washington Martins Pontes, Cristiane M Milanezi, Paulo Marcos da Mata Guedes, Wanderson Geraldo de Lima, Richard Schulz, João Santana da Silva, Andre Talvani
Chemokines (CKs) and chemokine receptors (CKR) promote leukocyte recruitment into cardiac tissue infected by the Trypanosoma cruzi. This study investigated the long-term treatment with subantimicrobial doses of doxycycline (Dox) in association, or not, with benznidazole (Bz) on the expression of CK and CKR in cardiac tissue. Thirty mongrel dogs were infected, or not, with the Berenice-78 strain of T. cruzi and grouped according their treatments: (i) two months after infection, Dox (50 mg/kg) 2x/day for 12 months; (ii) nine months after infection, Bz (3,5 mg/kg) 2x/day for 60 days; (iii) Dox + Bz; and (iv) vehicle...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27662792/altered-circulating-t-follicular-helper-cell-subsets-in-patients-with-psoriasis-vulgaris
#20
Ying Wang, Lili Wang, Yanchao Shi, Feifei Wang, Haoyu Yang, Shuo Han, Yanping Bai
Circulating T follicular helper (Tfh) cells in the blood are counterparts to conventional Tfh cells in germinal centres. Similarly to conventional Tfh cells, circulating Tfh cells provide helpful signals for B cells. Circulating Tfh cells can be divided into three subpopulations, including Tfh17 (CXCR3-CCR6+), Tfh1 (CXCR3+CCR6-), and Tfh2 (CXCR3-CCR6-) cells, based on differences in CXCR3 and CCR6 expression. Recent studies have demonstrated that alterations in circulating Tfh cell subsets have significant effects on the progression of numerous autoimmune diseases...
September 20, 2016: Immunology Letters
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