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Lirong Liu, Wenhui Fan, He Zhang, Shuang Zhang, Liang Cui, Meng Wang, Xiaoyuan Bai, Wenxian Yang, Lei Sun, Limin Yang, Wenjun Liu, Jing Li
Interferon, a natural protein that is produced by a variety of cells during viral infection, activates the transcription of multiple functional genes in cells, regulates synergy among various signaling pathways, and mediates many biological functions such as antiviral activity, immune regulation, and cell growth. However, clinical research on interferon in livestock is lacking. In this study, recombinant porcine interferon (PoIFNα) was used as an adjuvant, in combination with inactivated influenza virus, to vaccinate 6-week-old pigs via nasal infusion...
April 15, 2019: Virologica Sinica
Huanyu Zhou, Li Xi, Daniel Ziemek, Shawn O'Neil, Julie Lee, Zachary Stewart, Yutian Zhan, Shanrong Zhao, Ying Zhang, Karen Page, Austin Huang, Mateusz Maciejewski, Baohong Zhang, Kenneth J Gorelick, Lori Fitz, Vivek Pradhan, Fabio Cataldi, Michael Vincent, David Von Schack, Kenneth Hung, Mina Hassan-Zahraee
BACKGROUND AND AIMS: To define pharmacodynamic and efficacy biomarkers in ulcerative colitis [UC] patients treated with PF-00547659, an anti-human mucosal addressin cell adhesion molecule-1 [MAdCAM-1] monoclonal antibody, in the TURANDOT study. METHODS: Transcriptome, proteome and immunohistochemistry data were generated in peripheral blood and intestinal biopsies from 357 subjects in the TURANDOT study. RESULTS: In peripheral blood, C-C motif chemokine receptor 9 [CCR9] gene expression demonstrated a dose-dependent increase relative to placebo, but in inflamed intestinal biopsies CCR9 gene expression decreased with increasing PF-00547659 dose...
March 19, 2019: Journal of Crohn's & Colitis
Hongmei Fu, Maryam Jangani, Aleesha Parmar, Guosu Wang, David Coe, Sarah Spear, Inga Sandrock, Melania Capasso, Mark Coles, Georgina Cornish, Helena Helmby, Federica M Marelli-Berg
Protective immunity relies upon differentiation of T cells into the appropriate subtype required to clear infections and efficient effector T cell localization to antigen-rich tissue. Recent studies have highlighted the role played by subpopulations of tissue-resident memory (TRM ) T lymphocytes in the protection from invading pathogens. The intestinal mucosa and associated lymphoid tissue are densely populated by a variety of resident lymphocyte populations, including αβ and γδ CD8+ intraepithelial T lymphocytes (IELs) and CD4+ T cells...
2019: Frontiers in Immunology
Sofie L M Blokland, Christina-Maria Flessa, Joel A G van Roon, Clio P Mavragani
In primary SS (pSS), chemokines and cytokines orchestrate immunopathology driven by a complex network of interacting inflammatory cells. In recent years, the importance of chemotactic and non-chemotactic cytokines that control function, movement and placing of all cells within the inflamed exocrine glands and directing immunopathology has become increasingly clear. This paper reviews the current knowledge on chemokines and focuses on the emerging roles of novel chemotactic and non-chemotactic mediators in pSS...
March 5, 2019: Rheumatology
Jayaum S Booth, Eric Goldberg, Seema A Patil, Bruce D Greenwald, Marcelo B Sztein
CD4+ and CD8+ T subsets are essential components of the adaptive immune system which act in concert at the site of infections to effectively protect against pathogens. Very limited data is available in humans regarding the relationship between CD4+ and CD8+ S. Typhi responsive cells in the terminal ileum mucosa (TI) and peripheral blood following Ty21a oral typhoid immunization. Here, we compared TI lamina propria mononuclear cells (LPMC) and peripheral blood CD4+ and CD8+ T memory (TM ) subsets responses and their relationship by Spearman's correlation following Ty21a immunization in volunteers undergoing routine colonoscopy...
March 6, 2019: Human Vaccines & Immunotherapeutics
Atsushi Kadowaki, Ryoko Saga, Youwei Lin, Wakiro Sato, Takashi Yamamura
The mechanism underlying the progression of relapsing-remitting multiple sclerosis to secondary progressive multiple sclerosis (SPMS), characterized by accumulating fixed disability, is yet to be fully understood. Although alterations in the gut microbiota have recently been highlighted in multiple sclerosis pathogenesis, the mechanism linking the altered gut environment with the remote CNS pathology remains unclear. Here, we analyse human CD4+ memory T cells expressing the gut-homing chemokine receptor CCR9 and found a reduced frequency of CCR9+ memory T cells in the peripheral blood of patients with SPMS relative to healthy controls...
February 15, 2019: Brain
Matteo Basilissi, Camilla Tincati, Esther Merlini, Giuseppe Ancona, Elisa Borghi, Francesca Borgo, Alessandra Barassi, Antonella d'Arminio Monforte, Giulia Marchetti
HIV infection causes the progressive depletion of CD4+ T-lymphocytes and profound modifications of T-cell homeostasis, which persist despite virologically-suppressive treatment and have been linked to a worse clinical outcome. Enduring alterations of the gastrointestinal tract may represent the underlying pathogenic mechanisms of these phenomena. Twenty-six HIV-infected subjects were assessed over a 12-month period following the introduction of antiretroviral therapy. 18 uninfected individuals were enrolled as controls...
2019: PloS One
Eamy Nursaliza Yaacob, Bruno G De Geest, Jens Goethals, Aline Bajek, Kristof Dierckens, Peter Bossier, Daisy Vanrompay
Vibrio anguillarum causes high mortality in European sea bass (Dicentrarchus labrax) larviculture. In this study, we evaluated if the recombinant sea bass ferritin-H could stimulate the innate immune system of gnotobiotic European sea bass larvae resulting in protection against a V. anguillarum challenge. We also evaluated the effect of a V. anguillarum infection on the transcription of immune-related genes in gnotobiotic European sea bass larvae. Recombinant sea bass ferritin-H was produced, encapsulated in calcium alginate microparticles and orally delivered to sea bass larvae at seven days after hatching...
October 2018: Veterinary Immunology and Immunopathology
Yan Li, Shihao Chen, Yafei Chi, Yiran Yang, Xiwen Chen, Huating Wang, Zhe Lv, Jingjing Wang, Linjie Yuan, Ping Huang, Kewu Huang, Chris J Corrigan, Wei Wang, Sun Ying
ILC2s are implicated in asthma pathogenesis, but little is known about the mechanisms underlying their accumulation in airways. We investigated the time course of ILC2 accumulation in different tissues in murine models of asthma induced by a serial per-nasal challenge with ovalbumin (OVA), house dust mice (HDM), IL-25 and IL-33 and explored the potential roles of ILC2-attracting chemokines in this phenomenon. Flow cytometry was used to enumerate ILC2s at various time points. The effects of cytokines and chemokines on ILC2 migration were measured in vitro using a chemotaxis assay and in vivo using small animal imaging...
November 22, 2018: Cellular & Molecular Immunology
Ya Sun, Jun Shao, Feizhou Jiang, Yanqiu Wang, Qin Yan, Na Yu, Jin Zhang, Jie Zhang, Mingqing Li, Yinyan He
PROBLEM: Endometriosis (EM) is a chronic immunoinflammatory disease associated with an abnormal immunotolerant microenvironment. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that play a major role in immunosuppression in cancer, inflammation and other diseases. This paper aims to elucidate whether or not MDSCs are involved in regulating this microenvironment in EM and how this regulation occurs. METHOD OF STUDY: Immunochemistry (IHC) and qPCR were conducted to measure CD11b and ARG1 expression in the ectopic endometrium samples from EM patients...
October 30, 2018: American Journal of Reproductive Immunology: AJRI
Jacob Spinnen, Jochen Ringe, Michael Sittinger
Due to its chemoattraction potential on mesenchymal stromal cells of the CCL25/CCR9 axis, local application of CCL25 to severely damaged tissues may be a promising approach for regenerative therapies. Analysis of the given data revealed that CCL25/CCR9 signaling has a crucial role in regulation of an adult immune homeostasis. CCR9 expression variations resulted in dysfunctional immune response in colitis, rheumatoid arthritis and endometriosis. Regarding oncology, different neoplastic tissues exploit CCL25-dependent CCR9 signaling for either local proliferation or migration processes...
October 2018: Regenerative Medicine
Natalia V Ortiz Zacarías, Jacobus P D van Veldhoven, Laura Portner, Eric van Spronsen, Salviana Ullo, Margo Veenhuizen, Wijnand J C van der Velden, Annelien J M Zweemer, Roy M Kreekel, Kenny Oenema, Eelke B Lenselink, Laura H Heitman, Adriaan P IJzerman
The recent crystal structures of CC chemokine receptors 2 and 9 (CCR2 and CCR9) have provided structural evidence for an allosteric, intracellular binding site. The high conservation of residues involved in this site suggests its presence in most chemokine receptors, including the close homologue CCR1. By using [3 H]CCR2-RA-[ R], a high-affinity, CCR2 intracellular ligand, we report an intracellular binding site in CCR1, where this radioligand also binds with high affinity. In addition, we report the synthesis and biological characterization of a series of pyrrolone derivatives for CCR1 and CCR2, which allowed us to identify several high-affinity intracellular ligands, including selective and potential multitarget antagonists...
October 25, 2018: Journal of Medicinal Chemistry
Tamara Pérez-Jeldres, Christopher J Tyler, Joshua D Boyer, Thangaraj Karuppuchamy, Giorgos Bamias, Parambir S Dulai, Brigid S Boland, William J Sandborn, Derek R Patel, Jesús Rivera-Nieves
After 20 years of successful targeting of pro-inflammatory cytokines for the treatment of IBD, an alternative therapeutic strategy has emerged, based on several decades of advances in understanding the pathogenesis of IBD. The targeting of molecules involved in leukocyte traffic has recently become a safe and effective alternative. With 2 currently approved drugs (ie, natalizumab, vedolizumab) and several others in phase 3 trials (eg, etrolizumab, ozanimod, anti-MAdCAM-1), the blockade of trafficking molecules has firmly emerged as a new therapeutic era for IBD...
August 24, 2018: Inflammatory Bowel Diseases
Z Vrablicova, K Soltys, A Krajcovicova, I Sturdik, T Koller, M Huorka, J Payer, S Stuchlik, Z Killinger, P Jackuliak, M Stuchlikova, H Drahovska, T Hlavaty
The aim of this study was to analyze the influence of 25(OH)VD serum concentration on the expression of mRNA cytokines (IL-6, IL-8, IL-12, IL-17, IL-23, TNFα, CCR1, CCR2, CCR5, CCR9, CCL5, TLR2, TLR4, TLR5, CD207 ,CD206, FoxP3) in mucosa of IBD patients. The cohort consisted of 86 IBD patients (48 CD and 38 UC) followed at the IBD center of University Hospital Bratislava-Ruzinov. We performed colonoscopy in each patient and took biopsies from mucosa of sigma and terminal ileum. Serum concentration of 25(OH)VD was assessed at the time of colonoscopy...
2018: Bratislavské Lekárske Listy
Palak J Trivedi, David H Adams
The principal targets for anti-chemokine therapy in inflammatory bowel disease (IBD) have been the receptors CCR9 and CXCR3 and their respective ligands CCL25 and CXCL10. More recently CCR6 and its ligand CCL20 have also received attention, the expression of the latter in enterocytes being manipulated through Smad7 signalling. These pathways, selected based on their fundamental role in regulating mucosal immunity, have led to the development of several therapeutic candidates that have been tested in early phase clinical trials with variable clinical efficacy...
August 22, 2018: Journal of Crohn's & Colitis
Zongguo Yang, Yuquan Tao, Xin Xu, Feng Cai, Yongchun Yu, Lifang Ma
OBJECTIVE: This study aimed to evaluate functions of APOBEC3F gene in biological process of hepatocellular carcinoma (HCC) and anti-tumor mechanisms of bufalin. METHODS: Effect of APOBEC3F and bufalin on cell proliferation and migration abilities were evaluated by CCK-8, wounding healing tests and transwell assays in SK-Hep1 and Bel-7404 cells. Bioinformatic analysis were also used to compare APOBEC3F expression levels, detect coexpressed genes and enrichment of pathways...
September 10, 2018: Biochemical and Biophysical Research Communications
Cong Wang, Zhenghuan Liu, Zhihui Xu, Xian Wu, Dongyang Zhang, Ziqi Zhang, Jianqin Wei
Chemokine ligand 25 (CCL25) and chemokine receptor 9 (CCR9) are important regulators of migration, proliferation and apoptosis in leukocytes and cancer cells. Blocking of the CCR9/CCL25 signal has been demonstrated to be a potential novel cancer therapy. Research into CCR9 and CCL25 has revealed their associated upstream and downstream signaling pathways; CCR9 is regulated by several immunological factors, including NOTCH, interleukin 2, interleukin 4 and retinoic acid. NOTCH in particular, has been revealed to be a crucial upstream regulator of CCR9...
August 2018: Oncology Letters
Yufei Xia, Jie Wu, Yiqun Du, Chunyu Miao, Zhiguo Su, Guanghui Ma
As peripheral lymphocytes are typically excluded from the gastrointestinal lymph tissues, current parenteral vaccinations fail to simultaneously induce systemic and mucosal responses. To break the natural barrier, "immunoticket" capsules are developed and heralded, which are designed with positive charged shells and oily core to spatiotemporally deliver antigens and all-trans retinoic acid (RA). After intramuscular vaccinations, these capsules function as an immunoticket to cultivate peripheral dendritic cells (DCs) with gut-homing receptors (CCR9)...
August 2018: Advanced Materials
Divyanshu Malhotra, Jimann Shin, Lilianna Solnica-Krezel, Erez Raz
Chemokines are secreted proteins that regulate a range of processes in eukaryotic organisms. Interestingly, different chemokine receptors control distinct biological processes, and the same receptor can direct different cellular responses, but the basis for this phenomenon is not known. To understand this property of chemokine signaling, we examined the function of the chemokine receptors Cxcr4a, Cxcr4b, Ccr7, Ccr9 in the context of diverse processes in embryonic development in zebrafish. Our results reveal that the specific response to chemokine signaling is dictated by cell-type-specific chemokine receptor signal interpretation modules (CRIM) rather than by chemokine-receptor-specific signals...
June 6, 2018: ELife
Francesco Ciccia, Giuliana Guggino, Michael Zeng, Ranjeny Thomas, Vidya Ranganathan, Arifur Rahman, Riccardo Alessandro, Aroldo Rizzo, Laura Saieva, Federica Macaluso, Sergio Peralta, Diana Di Liberto, Francesco Dieli, Paola Cipriani, Roberto Giacomelli, Dominique Baeten, Nigil Haroon
OBJECTIVE: Gut-derived innate lymphoid cell 3 (ILC3) has been shown to participate in the pathogenesis of ankylosing spondylitis (AS). CX3 CR1+ mononuclear phagocytes (MNPs) have been demonstrated to modulate ILC3 function in the gut. This study was undertaken to investigate the role of proinflammatory CX3 CR1+CD59+ MNPs in modulating ILC3 function in AS patients. METHODS: MNP subsets in the blood of AS patients and controls were analyzed by flow cytometry. The presence of CX3 CR1+CD59+ cells in tissue was confirmed by confocal microscopy...
December 2018: Arthritis & Rheumatology
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