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https://www.readbyqxmd.com/read/28228602/a-divergent-population-of-autoantigen-responsive-cd4-t-cells-in-infants-prior-to-%C3%AE-cell-autoimmunity
#1
Anne-Kristin Heninger, Anne Eugster, Denise Kuehn, Florian Buettner, Matthias Kuhn, Annett Lindner, Sevina Dietz, Sibille Jergens, Carmen Wilhelm, Andreas Beyerlein, Anette-G Ziegler, Ezio Bonifacio
Autoimmune diabetes is marked by sensitization to β cell self-antigens in childhood. We longitudinally followed at-risk children from infancy and performed single-cell gene expression in β cell antigen-responsive CD4(+) T cells through pre- and established autoimmune phases. A striking divergence in the gene signature of β cell antigen-responsive naïve CD4(+) T cells from children who developed β cell autoimmunity was found in infancy, well before the appearance of β cell antigen-specific memory T cells or autoantibodies...
February 22, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28224362/analysis-of-foxp3-regulatory-t-cell-subpopulations-in-peripheral-blood-and-tissue-of-patients-with-systemic-lupus-erythematosus
#2
Angelika Schmidt, Cosima C Rieger, Ram Kumar Venigalla, Szabolcs Éliás, Regina Max, Hanns-Martin Lorenz, Hermann-Josef Gröne, Peter H Krammer, Annegret Kuhn
Regulatory T cells (Tregs) are critical mediators of immune tolerance, yet their involvement in the autoimmune disease systemic lupus erythematosus (SLE) is incompletely understood. We analyzed CD4(+) T cell subpopulations with Treg-related phenotypes and their association with disease activity in peripheral blood (PB) and tissues of patients with SLE. In detail, we quantified subpopulations regarding CD25, FOXP3, CD62L, CCR6, CD27, CD45RA, and CD45RO expression in PB from 31 patients with SLE divided into two disease activity groups and 32 healthy controls using flow cytometry...
February 21, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28209402/chemokine-receptor-patterns-and-right-heart-failure-in-mechanical-circulatory-support
#3
Aditi Nayak, Colin Neill, Robert L Kormos, Luigi Lagazzi, Indrani Halder, Charles McTiernan, Jennifer Larsen, Ana Inashvili, Jeffrey Teuteberg, Timothy N Bachman, Karen Hanley-Yanez, Dennis M McNamara, Marc A Simon
BACKGROUND: Right ventricular failure (RVF) complicates 9% to 44% of left ventricular assist device (LVAD) implants post-operatively. Current prediction scores perform only modestly in validation studies, and do not include immune markers. Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. In this study we investigated chemokine receptor regulation in LVAD recipients who develop RVF. METHODS: Expression of chemokine receptor (CCR) genes 3 to 8 were examined in the peripheral blood of 111 LVAD patients, collected 24 hours before implant...
December 23, 2016: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28206670/altered-expression-of-cxcr3-and-ccr6-and-their-ligands-in-htlv-1-carriers-and-ham-tsp-patients
#4
Houshang Rafatpanah, Mehdi Felegari, Mahmoud Reza Azarpazhooh, Rosita Vakili, Taraneh Rajaei, Ian Hampson, Golmahossein Hassanshahi, Narges Valizadeh, Sina Gerayli, Hamid Farjifard, Shadi Zamanian, Farzad MollaHosseini, Seyed Abdolrahim Rezaee
Recruitment of leukocytes by chemokines and chemokine receptors to CNS plays a crucial role in the induction of inflammatory response in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). In the present study, chemokine and chemokine receptors involved in trafficking of lymphocytes to the CNS were measured in HAM/TSP patients, HTLV-1 asymptomatic carriers (ACs), and healthy controls. The PVL, CCR6 and CXCR3 mRNA expression, and CXCL9 and CXCL10 protein levels were measured in all subjects...
February 16, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28188806/role-of-ccl20-mediated-immune-cell-recruitment-in-nf-%C3%AE%C2%BAb-mediated-trail-resistance-of-pancreatic-cancer
#5
Claudia Geismann, Frauke Grohmann, Anita Dreher, Robert Häsler, Philip Rosenstiel, Karen Legler, Charlotte Hauser, Jan Hendrik Egberts, Bence Sipos, Stefan Schreiber, Andreas Linkermann, Zonera Hassan, Günter Schneider, Heiner Schäfer, Alexander Arlt
Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers. From a clinical view, the transcription factor NF-κB is of particular importance, since this pathway confers apoptosis resistance and limits drug efficacy. Whereas the role of the most abundant NF-κB subunit p65/RelA in therapeutic resistance is well documented, only little knowledge of the RelA downstream targets and their functional relevance in TRAIL mediated apoptosis in PDAC is available. In the present study TRAIL resistant and sensitive PDAC cell lines were analyzed for differentially expressed RelA target genes, to define RelA downstream targets mediating TRAIL resistance...
February 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28183330/th17-and-cd24-hi-cd27-regulatory-b-lymphocytes-are-biomarkers-of-response-to-biologics-in-rheumatoid-arthritis
#6
Sarah Salomon, Caroline Guignant, Pierre Morel, Gauthier Flahaut, Clément Brault, Clément Gourguechon, Patrice Fardellone, Jean-Pierre Marolleau, Brigitte Gubler, Vincent Goëb
BACKGROUND: The aim was to describe the regulatory B and T cells (Breg and Treg) and T helper 17 (Th17) lymphocytes before and under treatment with biologic drugs, and to assess their potential predictive value as biomarkers of response in rheumatoid arthritis (RA). METHODS: This was a non-randomised, single-centre, prospective study. Patients with active RA (American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010) who required the initiation or switch to any biologic drug except rituximab were included...
February 10, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28179539/smoking-reduces-circulating-cd26-hi-cd161-hi-mait-cells-in-healthy-individuals-and-patients-with-multiple-sclerosis
#7
Cecilie Ammitzbøll, Lars Börnsen, Jeppe Romme Christensen, Rikke Ratzer, Birgitte Romme Nielsen, Helle B Søndergaard, Marina R von Essen, Finn Sellebjerg
Upon chronic cigarette smoke exposure, inhaled antigens and irritants cause altered lung immune homeostasis. Circulating immune cells are affected, and smoking is associated with an increased risk of developing various disorders, including multiple sclerosis (MS). This study was conducted to determine the impact of smoking on circulating immune cell subsets. Furthermore, we determined whether any smoking-associated changes were related to MS. With the use of flow cytometry, CFSE assays, and ELISpot assays, we analyzed circulating immune cell phenotypes and quantified antigen-induced proliferation and cytokine secretion in smokers and nonsmokers in a cohort of 100 healthy individuals (HI)...
February 8, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28141917/enhanced-bruton-s-tyrosine-kinase-activity-in-peripheral-blood-b-lymphocytes-of-autoimmune-disease-patients
#8
Odilia B J Corneth, Gwenny M P Verstappen, Sandra M J Paulissen, Marjolein J W de Bruijn, Jasper Rip, Melanie Lukkes, Jan Piet van Hamburg, Erik Lubberts, Hendrika Bootsma, Frans G M Kroese, And Rudi W Hendriks
OBJECTIVE: Bruton's tyrosine kinase (BTK) transmits crucial survival signals from the B cell receptor (BCR) in B cells. Pharmacological BTK inhibition effectively diminishes disease symptoms in mouse models of autoimmunity and, conversely, transgenic BTK overexpression induces systemic autoimmunity in mice. We investigated BTK expression and activity in human B cells in the context of autoimmune disease. METHODS: Using intracellular flow cytometry, we quantified BTK expression and phosphorylation in peripheral blood B cell subsets in patients with rheumatoid arthritis (RA; n=30) and primary Sjogren's Syndrome (pSS; n=26) and matched healthy controls...
January 31, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28115058/ccr6-is-dispensable-for-the-development-of-skin-lesions-induced-by-imiquimod-despite-its-effect-on-epidermal-homing-of-il-22-producing-cells
#9
Perrine M Cochez, Camille Michiels, Emilie Hendrickx, Nicolas Dauguet, Guy Warnier, Jean-Christophe Renauld, Laure Dumoutier
Expression of the chemokine receptor Ccr6 is shared by most IL-22 producing cells and Ccr6-deficient mice showed decreased IL-22 production and skin inflammation upon IL-23 intradermal injections. To determine whether this observation might be extended to another psoriasis model, we applied imiquimod on Ccr6-deficient mice. Whereas epidermal IL-22 production was decreased because of a deficient recruitment of γδ T cells in these mice, they were not protected against psoriatic lesions. When primary epidermis or dermis tissue culture cells from non-treated mice were stimulated ex vivo with IL-1α/IL-2/IL-23, we observed that Ccr6 is crucial for Il22 expression from epidermal but not dermal cultures...
January 20, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28051083/the-loss-of-ccr6-and-cd161-cd4-t-cell-homeostasis-contributes-to-disease-progression-in-siv-infected-rhesus-macaques
#10
C S McGary, X Alvarez, S Harrington, B Cervasi, E S Ryan, R I Iriele, S Paganini, J L Harper, K Easley, G Silvestri, A A Ansari, M Lichterfeld, L Micci, M Paiardini
Although previous studies have shown that CD4(+) T cells expressing CCR6 and CD161 are depleted from blood during HIV infection, the mechanisms underlying their loss remain unclear. In this study, we investigated how the homeostasis of CCR6(+) and CD161(+) CD4(+) T cells contributes to SIV disease progression and the mechanisms responsible for their loss from circulation. By comparing SIV infection in rhesus macaques (RMs) and natural host sooty mangabeys (SMs), we found that the loss of CCR6(+) and CD161(+) CD4(+) T cells from circulation is a distinguishing feature of progressive SIV infection in RMs...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28038358/il-22-promotes-fas-expression-in-oligodendrocytes-and-inhibits-foxp3-expression-in-t-cells-by-activating-the-nf-%C3%AE%C2%BAb-pathway-in-multiple-sclerosis
#11
Jin Zhen, Jun Yuan, Yongwang Fu, Runxiu Zhu, Meiling Wang, Hong Chang, Yan Zhao, Dong Wang, Zuneng Lu
Multiple sclerosis (MS) is characterized by an increase in interleukin-22 and Fas, and a decrease in FOXP3, among other factors. In this study, we examined patients with MS and healthy control subjects and used the experimental autoimmune encephalomyelitis (EAE) animal model to identify the effects of IL-22 on oligodendrocytes and T cells in MS development. In MS, the expression of Fas in oligodendrocytes and IL-22 in CD4(+)CCR4(+)CCR6(+)CCR10(+) T cells was enhanced. Ikaros and FOXP3 were both decreased in T cells...
December 27, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/28031342/transcriptional-classification-and-functional-characterization-of-human-airway-macrophage-and-dendritic-cell-subsets
#12
Vineet I Patel, J Leland Booth, Elizabeth S Duggan, Steven Cate, Vicky L White, David Hutchings, Susan Kovats, Dennis M Burian, Mikhail Dozmorov, Jordan P Metcalf
The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage. Six subsets of phagocytic APC (HLA-DR(+)) were consistently observed...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28025071/th17-cells-correlate-positively-to-the-structural-and-functional-integrity-of-the-brain-in-bipolar-depression-and-healthy-controls
#13
Sara Poletti, Harm de Wit, Elena Mazza, Annemarie J M Wijkhuijs, Clara Locatelli, Veronica Aggio, Cristina Colombo, Francesco Benedetti, Hemmo A Drexhage
: Abnormalities of T cell-mediated immune activation, in the absence of active somatic immune diseases, have consistently been reported in mood disorders. Apart from being important players in the regulation of cells of the immune system, T cells are essential for normal brain development. We here report studies on the relationship between circulating levels of T helper cells and structural and functional brain imaging in depressed bipolar patients. Since the CCL20-CCR6 axis is an important entry to the brain we differentiated the various T helper cell subpopulations on the basis of their chemokine receptor expression...
December 23, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28007920/role-of-il-32-in-hiv-reactivation-and-its-link-to-hiv-hsv-coinfection
#14
Pedro M M Mesquita, Paula Preston-Hurlburt, Marla J Keller, Nalini Vudattu, Lilia Espinoza, Michelle Altrich, Kathryn Anastos, Kevan C Herold, Betsy C Herold
BACKGROUND: HSV-2 exacerbates HIV by unclear mechanisms. These studies tested the impact of HSV-2 on systemic T cell populations and HIV reservoirs. METHODS: Peripheral blood mononuclear cells from HIV-infected women on antiretroviral therapy who were HSV-2 seropositive or seronegative (HIV(+)/HSV-2(+) or HIV(+)/HSV-2(-)) and HIV-uninfected controls were analyzed by flow cytometry. HIV cell-associated (CA)-DNA and RNA were quantified in the absence or presence of activating stimuli, recombinant IL-32γ, and a RUNX1 inhibitor...
December 22, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28005525/the-ccr6-ccl20-chemokine-axis-in-hiv-immunity-and-pathogenesis
#15
Adrian Yong Sing Lee, Heinrich Körner
Recent studies in human immunodeficiency virus (HIV) have garnered interest for the role of CC chemokine receptor 6 (CCR6) and its known ligands, CCL20 and human β-defensins, in viral entry, dissemination and anti-viral immunity. Several studies have suggested that CCR6 may also act as a weak co-receptor of HIV entry, in addition to the canonical CXCR4 and CCR5.However, the pathogenic significance has yet to be demonstrated as the observations for preferential infection of CD4+CCR6+ over CD4+CCR6¯ T cells appear to be independent of CCR6 expression...
December 21, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27987497/-significance-of-different-t-follicular-helper-subsets-in-rheumatoid-arthritis
#16
X M Chen, J Li, X Y Zhang, Y B Jin, D Yu, X L Sun, L J Wu, J He, Z G Li
OBJECTIVE: To detect the expressions of T follicular helper (Tfh) subsets and T follicular helper effect memory (Tfhem) cells in circulation of patients with rheumatoid arthritis (RA), as well as to examine their roles in providing biomarkers for active RA. METHODS: This study enrolled 41 patients with RA, who were navely-treated or had no application of hormone and disease-modifying anti-rheumatic drugs in recent 3 months, as well as 32 healthy controls. The percentages of Tfhem (CD4(+)CXCR5(+)CCR7(low)PD1(high)) cells, Tfh (CD3(+)CD4(+)CXCR5(+)CD45RA(-)) subsets, Tfh1 (CXCR3(+)CCR6(-)Tfh),Tfh2 (CXCR3(-)CCR6(-)Tfh),and Tfh17 (CXCR3(-)CCR6(+)Tfh), were determined by flow cytometry of peripheral blood from the patients with RA and health controls...
December 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27982014/monocyte-derived-inflammatory-langerhans-cells-and-dermal-dendritic-cells-mediate-psoriasis-like-inflammation
#17
Tej Pratap Singh, Howard H Zhang, Izabela Borek, Peter Wolf, Michael N Hedrick, Satya P Singh, Brian L Kelsall, Bjorn E Clausen, Joshua M Farber
Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6C(hi) blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27935859/histone-deacetylase-inhibitors-inhibit-metastasis-by-restoring-a-tumor-suppressive-microrna-150-in-advanced-cutaneous-t-cell-lymphoma
#18
Fumito Abe, Akihiro Kitadate, Sho Ikeda, Junsuke Yamashita, Hiroki Nakanishi, Naoto Takahashi, Chikara Asaka, Kazuaki Teshima, Tomomitsu Miyagaki, Makoto Sugaya, Hiroyuki Tagawa
Tumor suppressive microRNA (miR)-150 inhibits metastasis by combining with the C-C chemokine receptor 6 (CCR6) "seed sequence" mRNA of the 3'-untranslated region (3'-UTR) in advanced cutaneous T-cell lymphoma (CTCL). Because the histone deacetylase inhibitor (HDACI) vorinostat showed excellent outcomes for treating advanced CTCL, HDACIs may reduce the metastasis of CTCL by targeting miR-150 and/ or CCR6. To examine whether these candidate molecules are essential HDACI targets in advanced CTCL, we used the My-La, HH, and HUT78 CTCL cell lines for functional analysis because we previously demonstrated that their xenografts in NOD/Shi-scid IL-2γnul mice (CTCL mice) induced multiple metastases...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27933058/skewed-lung-ccr4-to-ccr6-cd4-t-cell-ratio-in-idiopathic-pulmonary-fibrosis-is-associated-with-pulmonary-function
#19
Ayodeji Adegunsoye, Cara L Hrusch, Catherine A Bonham, Mohammad R Jaffery, Kelly M Blaine, Meghan Sullivan, Matthew M Churpek, Mary E Strek, Imre Noth, Anne I Sperling
RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease. While it has been suggested that T cells may contribute to IPF pathogenesis, these studies have focused primarily on T cells outside of the pulmonary interstitium. Thus, the role of T cells in the diseased lung tissue remains unclear. OBJECTIVE: To identify whether specific CD4(+) T cell subsets are differentially represented in lung tissue from patients with IPF. METHODS: CD4(+) T cell subsets were measured in lung tissue obtained from patients with IPF at the time of lung transplantation, and from age- and gender-matched organ donors with no known lung disease...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27928019/toll-like-receptor-2-ligation-enhances-hiv-1-replication-in-activated-ccr6-cd4-t-cells-by-increasing-virus-entry-and-establishing-a-more-permissive-environment-to-infection
#20
Jean-François Bolduc, Michel Ouellet, Laurent Hany, Michel J Tremblay
: In this study, we investigated the effect of Toll-like receptor 2 (TLR2) ligation on the permissiveness of activated CD4(+) T cells to HIV-1 infection by focusing our experiments on the relative susceptibility of cell subsets based on their expression of CCR6. Purified primary human CD4(+) T cells were first subjected to a CD3/CD28 costimulation before treatment with the TLR2 agonist Pam3CSK4. Finally, cells were inoculated with R5-tropic HIV-1 particles that permit us to study the effect of TLR2 triggering on virus production at both population and single-cell levels...
February 15, 2017: Journal of Virology
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