Andrius Januskevicius, Egle Jurkeviciute, Ieva Janulaityte, Virginija Kalinauskaite-Zukauske, Skaidrius Miliauskas, Kestutis Malakauskas
Eosinophils subtypes as lung-resident (rEOS) and inflammatory (iEOS) eosinophils are different in surface protein expression, functions, response to IL-5 and localization in lungs. rEOS- and iEOS-like eosinophils are found in blood; thus, we aimed to investigate their quantity and survivability in asthma patients. A total of 40 individuals were included: 10 steroid-free non-severe allergic asthma (AA), and 18 severe non-allergic eosinophilic asthma (SNEA) patients, the control group consisted of 12 healthy non-smoking subjects (HS)...
May 18, 2020: Cells
Abhimanyu A Amarnani, Katlin R Poladian, Beatriz E Marciano, Janine R Daub, Sandra G Williams, Alicia A Livinski, Amy P Hsu, Cindy L Palmer, Cara M Kenney, Daniele N Avila, Steven M Holland, James D Katz
PURPOSE: To characterize rheumatological manifestations of GATA2 deficiency. METHODS: Single-center, retrospective review of 157 patients with GATA2 deficiency. Disease course, laboratory results, and imaging findings were extracted. In-person rheumatological assessments were performed on selected, available patients. A literature search of four databases was conducted to identify additional cases. RESULTS: Rheumatological findings were identified in 28 patients, out of 157 cases reviewed (17...
May 20, 2020: Scientific Reports
Martin Eichmann, Roman Baptista, Richard J Ellis, Susanne Heck, Mark Peakman, Craig A Beam
We previously reported that costimulation blockade by abatacept limits the decline of β-cell function and the frequency of circulating CD4+ central memory T cells (TCM ) (CD45RO+ CD62L+ ) in new-onset type 1 diabetes. In human subjects receiving placebo, we found a significant association between an increase in CD4+ TCM cells and the decline of β-cell function. To extend and refine these findings, we examined changes in human CD4+ and CD8+ naive and memory T cell subsets at greater resolution using polychromatic flow and mass cytometry...
May 13, 2020: Journal of Immunology
Shuaichen Li, Jiafeng Ding, Lihong Jiang, Muhammad Abid Hayat, Qiaozhi Song, Yuepeng Li, Xianhao Zhang, Jiantao Zhang
Alimentary oligofructose (OF) overload can induce several diseases in cattle, such as ruminal acidosis, laminitis, and synovitis. The role of blood polymorphonuclear neutrophil (PMN) remains unclear during OF overload. The aim of this study was to investigate the dynamic changes in reactive oxygen species (ROS) production and the expression profile of genes in blood PMN in a model of OF overload. Twelve clinically healthy and non-pregnant Chinese Holstein heifers, aged between 18 and 26 mo, weighing 335-403 kg, BCS (5-point scale) ranges 2...
2020: Frontiers in Veterinary Science
Hannah K Drescher, Angela Schippers, Stefanie Rosenhain, Felix Gremse, Laura Bongiovanni, Alain de Bruin, Sreepradha Eswaran, Suchira U Gallage, Dominik Pfister, Marta Szydlowska, Mathias Heikenwalder, Sabine Weiskirchen, Norbert Wagner, Christian Trautwein, Ralf Weiskirchen, Daniela C Kroy
CD62L (L-Selectin) dependent lymphocyte infiltration is known to induce inflammatory bowel disease (IBD), while its function in the liver, especially in non-alcoholic steatohepatitis (NASH), remains unclear. We here investigated the functional role of CD62L in NASH in humans as well as in two mouse models of steatohepatitis. Hepatic expression of a soluble form of CD62L (sCD62L) was measured in patients with steatosis and NASH. Furthermore, CD62L-/- mice were fed with a methionine and choline deficient (MCD) diet for 4 weeks or with a high fat diet (HFD) for 24 weeks...
April 29, 2020: Cells
Alex R Jenkins, Neil S Holden, Luke P Gibbons, Arwel W Jones
Frequent exacerbators of Chronic Obstructive Pulmonary Disease (COPD) is a distinct clinical phenotype characterised by systemic inflammation. Study objectives were to determine clinical outcomes of pulmonary rehabilitation in frequent exacerbators and the impact this has on the key surrogate markers of this phenotype. Eighty-five mild-very severe COPD patients (FEV1 pred, 52 ± 18%) were categorised as frequent (≥2 exacerbations per year, n  = 50) or infrequent exacerbators (≤1 exacerbation per year, n  = 35)...
May 3, 2020: COPD
Xiao Wang, Yaxian Gao, Xiaoqing Zhang, Xiaonan Wang, Biao Wang, Xin Meng, Yasunobu Yoshikai, Yuanyuan Wang, Xun Sun
Inflammatory bowel disease is one of the major causes of colitis-associated colon cancer (CAC). Therefore, it is necessary to explore new therapies to prevent colon cancer (CRC) in view of the relationship between chronic inflammation and tumor development. Previous studies on the correlation between CD30L/CD30 and cancer were mostly limited to lymphoid or homogenous tumors, while there have been only a few reports on the role of CD30L/CD30 signal transduction in the pathogenesis of CAC. In this study, we established an AOM/DSS-induced CAC model with CD30LKO mice to explore the effect of CD30L/CD30 signal transduction on the formation of the intestinal tumor immune microenvironment (TIME) during the development of intestinal tumors...
April 27, 2020: International Immunopharmacology
Fabio Casciano, Marco Diani, Andrea Altomare, Francesca Granucci, Paola Secchiero, Giuseppe Banfi, Eva Reali
The chemokine receptor CCR4 has emerged as a skin-homing molecule important for the migration of T cells from the blood to the dermis. From our previous data on psoriasis patients, CCR4+ memory T cells emerged as a putative recirculating population between skin and blood. Here we focused our attention on the expression of CCR4 and skin-tropic molecules in the different stages of memory T cell differentiation. We analyzed the chemokine receptor profile in CD8+ and CD4+ CD45RA- CCR7+ (TCM ) and CD45RA- CCR7- (TEM ) cells...
2020: Frontiers in Immunology
Denise Risnik, Esteban E Elías, Irene Keitelman, Ana Colado, Enrique Podaza, Gregorio Cordini, Maricef Vergara Rubio, Horacio Fernández Grecco, Raimundo Fernando Bezares, Mercedes Borge, Analía Trevani, Mirta Giordano, Carolina Jancic, Romina Gamberale
Ibrutinib is a BTK/ITK inhibitor with efficacy for the treatment of various lymphoid cancers, including CLL. Considering that innate and adaptative immune defects are a dominant feature of CLL patients, we evaluated whether in vitro ibrutinib affects the survival and function of neutrophils and γδ T cells, key players of the early immune response against microbes. Neutrophils and γδ T cells were obtained from peripheral blood of healthy donors and CLL patients. We found that ibrutinib reduces the production of reactive oxygen species (ROS) and bacteria killing capacity, and slightly impairs neutrophil extracellular traps (NETs) production without affecting bacteria-uptake and CD62L-downregulation induced by fMLP or aggregated IgG...
April 19, 2020: Leukemia & Lymphoma
Inês T Freitas, Willard Tinago, Hirofumi Sawa, Julie McAndrews, Brenda Doak, Charlotte Prior-Fuller, Gerard Sheehan, John S Lambert, Eavan Muldoon, Aoife G Cotter, William W Hall, Patrick W G Mallon, Michael J Carr
BACKGROUND: The objectives of this study were to investigate the relationships between polymorphisms at the interferon lambda (IFNL) locus and CD4+ :CD8+ ratio normalisation in people living with HIV (PLWH) on effective antiretroviral therapy (ART); and to examine whether these polymorphisms influence the composition of T lymphocyte compartments in long-term treated HIV-1 infection. METHODS: A cross-sectional study in PLWH enrolled into the Mater Immunology study...
April 15, 2020: AIDS Research and Therapy
Matthew D Martin, Ramakrishna Sompallae, Christina S Winborn, John T Harty, Vladimir P Badovinac
Enhanced host protection against re-infection requires generation of memory T cells of sufficient quantity and functional quality. Unlike well-studied inbred mice, T cell responses of diverse size and quality are generated following infection of humans and outbred mice. Thus, additional models are needed that accurately reflect variation in immune outcomes in genetically diverse populations and to uncover underlying genetic causes. The Collaborative Cross (CC), a large recombinant inbred panel of mice, is an ideal model in this pursuit for the high degree of genetic variation present, because it allows for assessment of genetic factors underlying unique phenotypes...
April 14, 2020: Cell Reports
Jing Gong, Sanjeev Noel, Joshua Hsu, Errol L Bush, Lois J Arend, Mohanraj Sadasivam, Sul A Lee, Johanna T Kurzhagen, Abdel Rahim A Hamad, Hamid Rabb
Acute kidney injury (AKI) due to cisplatin is a significant problem that limits its use as an effective chemotherapeutic agent. TCR+CD4-CD8- double negative (DN) T cells constitute major T cell population in human and mouse kidney, express PD1 and protect from ischemic AKI. However, the pathophysiologic roles of DN T cells in cisplatin-induced AKI is unknown. In this study, wild type (WT) mice were treated with cisplatin (30mg/kg) or vehicle and the effect on kidney DN T cell numbers and function were measured...
April 13, 2020: American Journal of Physiology. Renal Physiology
David Kung-Chun Chiu, Vincent Wai-Hin Yuen, Jacinth Wing-Sum Cheu, Larry Lai Wei, Vox Ting, Michael Fehlings, Hermi Sumatoh, Alessandra Nardin, Evan W Newell, Irene Oi-Lin Ng, Thomas Chung-Cheung Yau, Chun-Ming Wong, Carmen Chak-Lui Wong
BACKGROUND & AIMS: Immune checkpoint inhibitors are effective in treatment of some hepatocellular carcinomas (HCCs), but these tumors do not always respond to inhibitors of programmed cell death 1 (PDCD1, also called PD1). We investigated mechanisms of resistance of liver tumors in mice to infiltrating T cells. METHODS: Mice were given hydrodynamic tail vein injections of CRISPR-Cas9 and transposon vectors to disrupt Trp53 and overexpress Myc (Trp53KO /C-MycOE mice)...
April 7, 2020: Gastroenterology
Mieke Metzemaekers, Sofie Vandendriessche, Nele Berghmans, Mieke Gouwy, Paul Proost
CXCL8 is the principal human neutrophil-attracting chemokine and a major mediator of inflammation. The chemokine exerts its neutrophil-chemotactic and neutrophil-activating activities via interaction with glycosaminoglycans (GAGs) and activation of the G protein-coupled receptors (GPCRs) CXCR1 and CXCR2. Natural CXCL8 displays an exceptional degree of amino (NH2 )-terminal heterogeneity. Most CXCL8 forms result from proteolytic processing of authentic CXCL8(1-77). Here, we compared the potencies to activate and recruit neutrophils of the 3 most abundant natural CXCL8 forms: full-length 77 amino acid CXCL8 and the 2 major natural truncated forms lacking 5 or 8 NH2 -terminal amino acids...
April 9, 2020: Journal of Leukocyte Biology
Tomas Kalina, Marina Bakardjieva, Maartje Blom, Martin Perez-Andres, Barbara Barendregt, Veronika Kanderová, Carolien Bonroy, Jan Philippé, Elena Blanco, Ingrid Pico-Knijnenburg, Jitse H M P Paping, Beata Wolska-Kuśnierz, Malgorzata Pac, Jakub Tkazcyk, Filomeen Haerynck, Himmet Haluk Akar, Renata Formánková, Tomáš Freiberger, Michael Svatoň, Anna Šedivá, Sonia Arriba-Méndez, Alberto Orfao, Jacques J M van Dongen, Mirjam van der Burg
The EuroFlow PID consortium developed a set of flow cytometry tests for evaluation of patients with suspicion of primary immunodeficiency (PID). In this technical report we evaluate the performance of the SCID-RTE tube that explores the presence of recent thymic emigrants (RTE) together with T-cell activation status and maturation stages and discuss its applicability in the context of the broader EuroFlow PID flow cytometry testing algorithm for diagnostic orientation of PID of the lymphoid system. We have analyzed peripheral blood cells of 26 patients diagnosed between birth and 2 years of age with a genetically defined primary immunodeficiency disorder: 15 severe combined immunodeficiency (SCID) patients had disease-causing mutations in RAG1 or RAG2 ( n = 4, two of them presented with Omenn syndrome), IL2RG ( n = 4, one of them with confirmed maternal engraftment), NHEJ1 ( n = 1), CD3E ( n = 1), ADA ( n = 1), JAK3 ( n = 3, two of them with maternal engraftment) and DCLRE1C ( n = 1) and 11 other PID patients had diverse molecular defects [ ZAP70 ( n = 1), WAS ( n = 2), PNP ( n = 1), FOXP3 ( n = 1), del22q11...
2020: Frontiers in Immunology
R Pitaksalee, A N Burska, S Ajaib, J Rogers, R Parmar, K Mydlova, X Xie, A Droop, J S Nijjar, P Chambers, P Emery, R Hodgett, I B McInnes, F Ponchel
BACKGROUND: The genetic risk associated with rheumatoid arthritis (RA) includes genes regulating DNA methylation, one of the hallmarks of epigenetic re-programing, as well as many T-cell genes, with a strong MHC association, pointing to immunogenetic mechanisms as disease triggers leading to chronicity. The aim of our study was to explore DNA methylation in early, drug-naïve RA patients, towards a better understanding of early events in pathogenesis. RESULT: Monocytes, naïve and memory CD4+ T-cells were sorted from 6 healthy controls and 10 RA patients...
April 7, 2020: Clinical Epigenetics
Syh-Jae Lin, Chien-Ya Hsu, Ming-Ling Kuo, Pei-Tzu Lee, Hsiu-Shan Hsiao, Ji-Yih Chen
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and joint destruction. Previous studies have shown that natural killer (NK) cells may play an important role in the pathogenesis of RA. Interleukin (IL)-15, a pro-inflammatory cytokine which induces proliferation and differentiation of NK cells, is overexpressed in RA. In this present study, we examine various NKRs and adhesion molecule expression on NK cells from RA patients and their response to IL-15 stimulation. We also sought to study cytokine-induced memory-like (CIML) NK cells in RA patients...
April 3, 2020: Scientific Reports
Junya Ichikawa, Tatsuya Yoshida, Ariel Isser, Andressa S Laino, Melinda Vassallo, David Woods, Sojung Kim, Mathias Oelke, Kristi Jones, Jonathan P Schneck, Jeffrey S Weber
PURPOSE: Generation of antigen-specific T cells from cancer patients employs large numbers of peripheral blood cells and/or tumor infiltrating cells to generate antigen-presenting and effector cells commonly requiring multiple rounds of re-stimulation ex vivo We used a novel paramagnetic, nanoparticle-based artificial antigen presenting cell (nano-aAPC) that combines anti-CD28 co-stimulatory and human MHC class I molecules that are loaded with antigenic peptides to rapidly expand tumor antigen-specific T cells from melanoma patients...
April 2, 2020: Clinical Cancer Research
Dan Song, Fangfang Qi, ShuaiShuai Liu, Zhongsheng Tang, Jinhai Duan, Zhibin Yao
We previously have reported that neonatal Bacillus Calmette-Guerin (BCG) vaccination improves neurogenesis and behavior in early life through affecting the neuroimmune milieu in the brain, but it is uncertain whether activation phenotypes and functional changes in T lymphocytes shape brain development. Here, we studied the effects of BCG vaccination via the adoptive transfer of T lymphocytes from the BALB/c wild-type mice into naive mice. Our results show that mice adoptive BCG-induced lymphocytes (BCG->naive mice) showed anxiolytic and antidepressant-like performance when completing an elevated plus maze (EPM) test...
2020: PloS One
F N Souza, M G Blagitz, C F Batista, P V Takano, R G Gargano, S A Diniz, M X Silva, J A Ferronatto, K R Santos, M B Heinemann, S De Vliegher, A M M P Della Libera
We analyzed a large number of immune response parameters from quarter milk samples with distinct bacteriological and quarter somatic cell count (qSCC) statuses. Furthermore, we sought to explore and identify displayed immune response patterns in milk samples from mammary glands with nonspecific mastitis. Thus, 92 quarter milk samples from 28 cows were stratified into 4 groups, as follows: (1) 49 culture-negative control quarters with a low qSCC (<1 × 105 cells/mL) from 19 dairy cows (so-called healthy quarters); (2) 15 culture-negative quarters with high qSCC (>2 × 105 cells/mL; so-called quarters with nonspecific mastitis) from 10 dairy cows; (3) 8 culture-positive quarters with low qSCC (noninflammatory quarters with low qSCC) from 5 dairy cows; and (4) 20 culture-positive quarters with high qSCC (so-called truly infected quarters) from 8 dairy cows...
March 27, 2020: Journal of Dairy Science
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