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Yusheng Cheng, Hui Li, Yinan Deng, Yan Tai, Kaining Zeng, Yingcai Zhang, Wei Liu, Qi Zhang, Yang Yang
Emerging evidence indicate that cancer-associated fibroblasts (CAFs) affect tumor progression by reshaping the tumor microenvironment. Neutrophils are prominent components of solid tumors and important in cancer progression. Whether the phenotype and function of neutrophils in hepatocellular carcinoma (HCC) are influenced by CAFs is not well understood. Herein, we investigated the effect of HCC-derived CAFs (HCC-CAFs) on the neutrophils and explored the biological role of this effect. We found that HCC-CAFs induced chemotaxis of neutrophils and protected them from spontaneous apoptosis...
March 19, 2018: Cell Death & Disease
Hanaa Safya, Amine Mellouk, Julie Legrand, Sylvain M Le Gall, Mohcine Benbijja, Colette Kanellopoulos-Langevin, Jean M Kanellopoulos, Pierre Bobé
A previous report has shown that regulatory T cells (Treg) were markedly more sensitive to adenosine-5'-triphosphate (ATP) than conventional T cells (Tconv). Another one has shown that Tregs and CD45RBlow Tconvs, but not CD45RBhigh Tconvs, displayed similar high sensitivity to ATP. We have previously reported that CD45RBlow Tconvs expressing B220/CD45RABC molecules in a pre-apoptotic stage are resistant to ATP stimulation due to the loss of P2X7 receptor (P2X7R) membrane expression. To gain a clearer picture on T-cell sensitivity to ATP, we have quantified four different cellular activities triggered by ATP in mouse T cells at different stages of activation/differentiation, in correlation with levels of P2X7R membrane expression...
2018: Frontiers in Immunology
Karin de Ruiter, Selma van Staveren, Bart Hilvering, Edward Knol, Nienke Vrisekoop, Leo Koenderman, Maria Yazdanbakhsh
Upon activation granulocytes upregulate several adhesion molecules (CD11b) and granule proteins (CD35, CD66b) and shed surface l-selectin (CD62L). These changes in expression, as assessed by flow cytometry, can be used as markers for activation. Whereas these markers are usually studied in fresh blood samples, a new method is required when samples are collected at a field site with no direct access to a flow cytometer. Therefore, we developed and tested a field-applicable method in which fixed leukocytes were cryopreserved...
March 13, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
Eanna P Connaughton, Serika Naicker, Shirley A Hanley, Stephanie M Slevin, John K Eykelenboom, Noel F Lowndes, Timothy O'Brien, Rhodri Ceredig, Matthew D Griffin, Michael C Dennedy
Human blood monocytes are sub-classified as classical, intermediate and non-classical. In this study, it was shown that conventionally-defined human intermediate monocytes (IM) can be divided into two distinct subpopulations with mid- and high-level surface expression of HLA-DR (referred to as DRmid and DRhi IM). These IM subpopulations were phenotypically and functionally characterized in healthy adult blood by flow cytometry, migration assays and lipoprotein uptake assays. Their absolute numbers and proportions were then compared in blood samples from obese and non-obese adults...
March 5, 2018: Immunology and Cell Biology
Cynthia Magro, Ruifeng Guo, Giang Huong Nguyen, Hamilton Tsang, Shabnam Momtahen
BACKGROUND: Lymphomatoid drug reactions can mimic endogenous T and B cell lymphoproliferative diseases. OBJECTIVES: We present a novel form of cutaneous drug reaction with features of pityriasis lichenoides (PL), a recognized form of T cell dyscrasia. METHODS: Ten cases were studied where a cutaneous eruption exhibiting semblance to PL within a few weeks to months after starting a particular drug. RESULTS: The patient cohort comprised 7 females and 3 males with the mean age of 60 years...
November 15, 2017: Dermatology Online Journal
Nienke M Ter Haar, Tamar Tak, Michal Mokry, Rianne C Scholman, Jenny M Meerding, Wilco de Jager, Anouk Verwoerd, Dirk Foell, Thomas Vogl, Johannes Roth, Pieter H C Leliefeld, Jorg van Loosdregt, Leo Koenderman, Sebastiaan J Vastert, Sytze de Roock
OBJECTIVE: Neutrophils are the most abundant innate immune cells in the blood, however little is known about their role in (acquired) chronic autoinflammatory diseases. We investigated neutrophils in systemic onset Juvenile Idiopathic Arthritis (sJIA), a prototypical multifactorial autoinflammatory disease, characterized by arthritis and severe systemic inflammation. METHODS: We analyzed 50 sJIA patients at disease onset and during remission on recombinant IL-1 receptor antagonist (rIL-1RA, anakinra)...
February 9, 2018: Arthritis & Rheumatology
Navid Dashti, Mahdi Mahmoudi, Farhad Gharibdoost, Hoda Kavosi, Ramazan Rezaei, Vahideh Imeni, Ahmadreza Jamshidi, Saeed Aslani, Shayan Mostafaei, Mohammad Vodjgani
Systemic sclerosis (SSc), an autoimmune disease of connective tissue, is characterized by inflammation, fibrosis, and vessel endothelial damage. Products of Integrin subunit beta 2 (ITGB2) and selectin L (SELL) genes participate in several functional pathways of immune system. The aim of this investigation was to survey the transcript level of ITGB2 and SELL genes as well as methylation status of CpG sites in promoter region of differently expressed gene in PBMCs of SSc patients. PBMCs were isolated from whole blood of 50 SSc patients and 30 healthy controls...
January 22, 2018: Rheumatology International
Ngoc Pham Minh, Satoshi Murata, Naomi Kitamura, Tomoyuki Ueki, Masatsugu Kojima, Toru Miyake, Katsushi Takebayashi, Hirokazu Kodama, Eiji Mekata, Masaji Tani
Adoptive cell transfer (ACT) is an emerging and promising cancer immunotherapy that has been improved through various approaches. Here, we described the distinctive characteristics and functions of tumor Ag-specific effector CD8+ T-cells, co-cultured with a tumor specific peptide and a stimulatory anti-OX40 antibody, before being used for ACT therapy in tumor-bearing mouse recipients. Splenic T-cells were obtained from wild-type FVB/N mice that had been injected with a HER2/neu (neu)-expressing tumor and a neu-vaccine...
January 4, 2018: International Journal of Cancer. Journal International du Cancer
Kalahe Hewage Iresha Nadeeka Madushani Herath, Jeong Ha Lee, Jinhee Cho, Areum Kim, Su Min Shin, Bohyung Kim, You-Jin Jeon, Youngheun Jee
BACKGROUND: Porphyra yezoensis is a red algae consumed mainly in Korea, Japan, and China for food. In the present study, we studied the immunological effect of pepsin extract of P. yezoensis (PPEE) on murine splenocytes. RESULTS: PPEE was not toxic on murine splenocytes and dramatically increased the proliferation of splenocytes compared to untreated control. Flow cytometry assay performed to sum up the effect of PPEE (31.3 and 62.5 μg/ml) on major immune cells revealed that PPEE had no effect on the function of CD3e+ CD4+ T-helper cells, CD3e+ CD8+ T-cytotoxic cells, CD44+ CD62L- effector T cells in splenocytes compared to untreated control...
December 27, 2017: Journal of the Science of Food and Agriculture
Sumie Fujii, Yasuo Miura, Aya Fujishiro, Takero Shindo, Yutaka Shimazu, Hideyo Hirai, Hidetoshi Tahara, Akifumi Takaori-Kondo, Tatsuo Ichinohe, Taira Maekawa
A substantial proportion of patients with acute graft-versus-host disease (aGVHD) respond to cell therapy with culture-expanded human bone marrow mesenchymal stromal/stem cells (BM-MSCs). However, the mechanisms by which these cells can ameliorate aGVHD-associated complications remain to be clarified. We show here that BM-MSC-derived extracellular vesicles (EVs) recapitulated the therapeutic effects of BM-MSCs against aGVHD. Systemic infusion of human BM-MSC-derived EVs prolonged the survival of mice with aGVHD and reduced the pathologic damage in multiple GVHD-targeted organs...
December 14, 2017: Stem Cells
Marta Consuegra-Fernández, Marc Julià, Mario Martínez-Florensa, Fernando Aranda, Cristina Català, Noelia Armiger-Borràs, María-Teresa Arias, Francisca Santiago, Antonio Guilabert, Anna Esteve, Carlos Muñoz, Carlos Ferrándiz, José-Manuel Carrascosa, Edurne Pedrosa, Jorge Romaní, Mercè Alsina, José-Manuel Mascaró-Galy, Francisco Lozano
Psoriasis is a chronic inflammatory skin disease with a strong genetic background and is triggered by environmental factors. Available evidence supports CD6, a lymphocyte surface receptor mostly expressed by T cells, as a putative target in autoimmunity. Accordingly, a humanized anti-CD6 antibody has been assayed for the treatment of certain autoimmune disorders, including psoriasis. Here, we present novel evidence in mice and humans for a direct involvement of CD6 in psoriasis pathophysiology. First, an attenuated form of imiquimod-induced psoriasis-like skin inflammation was demonstrated in CD6-deficient mice, as deduced from lower epidermal thickness and local reduced production of pro-inflammatory cytokines, namely, interleukin-17A...
December 11, 2017: Cellular & Molecular Immunology
Christopher A Klebanoff, Joseph G Crompton, Anthony J Leonardi, Tori N Yamamoto, Smita S Chandran, Robert L Eil, Madhusudhanan Sukumar, Suman K Vodnala, Jinhui Hu, Yun Ji, David Clever, Mary A Black, Devikala Gurusamy, Michael J Kruhlak, Ping Jin, David F Stroncek, Luca Gattinoni, Steven A Feldman, Nicholas P Restifo
Adoptive immunotherapies using T cells genetically redirected with a chimeric antigen receptor (CAR) or T cell receptor (TCR) are entering mainstream clinical practice. Despite encouraging results, some patients do not respond to current therapies. In part, this phenomenon has been associated with infusion of reduced numbers of early memory T cells. Herein, we report that AKT signaling inhibition is compatible with CAR and TCR retroviral transduction of human T cells while promoting a CD62L-expressing central memory phenotype...
December 7, 2017: JCI Insight
Feifei Qiu, Huazhen Liu, Chun-Ling Liang, Golay D Nie, Zhenhua Dai
Due to vigorous alloimmunity, an allograft is usually rejected without any conventional immunosuppressive treatment. However, continuous global immunosuppression may cause severe side effects, including tumors and infections. Mounting evidence has shown that cyclosporine (CsA), a common immunosuppressant used in clinic, impedes allograft tolerance by dampening regulatory T cells (Tregs), although it inhibits allograft rejection at the same time. Therefore, it is necessary to seek an alternative immunosuppressive drug that spares Tregs with high efficiency in suppression but low toxicity...
2017: Frontiers in Immunology
Xia Yang, Bo Huo, Xiaoning Zhong, Wenyan Su, Wenting Liu, Yumei Li, Zhiyi He, Jing Bai
Human regulatory T cells (Tregs) have been reported to be not significantly different in the peripheral blood of patients with chronic obstructive pulmonary disease (COPD) and healthy controls. Recent research has identified some new markers for Tregs and indicated that Tregs are composed of distinct subpopulations. The aim of the study was to describe the changing patterns of circulating Treg subpopulations in patients with acute exacerbation of COPD (AECOPD) and healthy controls, and to explore their potential roles in AECOPD pathogenesis...
December 2017: COPD
Alex Quach, Antonio Ferrante
The purification of human neutrophils for in vitro studies is challenging as they are easily activated through ex vivo manipulations. The technique of erythrocyte sedimentation combined with density gradient centrifugation remains widely practiced and was the subject of this study. Since in the sedimentation step the leukocytes are incubated with dextran, we have raised the likelihood that cellular activation would occur with mediator release leading to neutrophil activation. By comparing the activity of neutrophils purified from whole blood by the classical 2-step method of dextran sedimentation followed by low-density Ficoll-Hypaque (1...
2017: Journal of Immunology Research
Takeshi Susukida, Shigeki Aoki, Kotaro Kogo, Sota Fujimori, Binbin Song, Cong Liu, Shuichi Sekine, Kousei Ito
Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug reaction, potentially resulting in death. Although genome-wide association studies suggest that the occurrence of immune-mediated IDT is strongly associated with specific human leukocyte antigen (HLA) allotypes, these associations have not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice carrying chimeric HLA-B*57:01 (B*57:01-Tg) to determine if this in vivo model may be useful for evaluating immune-mediated IDT...
November 17, 2017: Archives of Toxicology
Justine K Nakiwala, Naomi F Walker, Collin R Diedrich, William Worodria, Graeme Meintjes, Robert J Wilkinson, Harriet Mayanja-Kizza, Robert Colebunders, Luc Kestens, Katalin A Wilkinson, David M Lowe
BACKGROUND: Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) remains incompletely understood. Neutrophils are implicated in tuberculosis pathology but detailed investigations in TB-IRIS are lacking. We sought to further explore the biology of TB-IRIS and in particular the role of neutrophils. SETTING: Two observational, prospective cohort studies in HIV/TB co-infected patients starting antiretroviral therapy, one to analyze gene expression and subsequently one to explore neutrophil biology...
November 6, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Kathleen M Gilbert, Sarah J Blossom, Brad Reisfeld, Stephen W Erickson, Kanan Vyas, Mary Maher, Brannon Broadfoot, Kirk West, Shasha Bai, Craig A Cooney, Sudeepa Bhattacharyya
Exposure to industrial solvent and water pollutant trichloroethylene (TCE) can promote autoimmunity, and expand effector/memory (CD62L) CD4(+) T cells. In order to better understand etiology reduced representation bisulfite sequencing was used to study how a 40-week exposure to TCE in drinking water altered methylation of ∼337 770 CpG sites across the entire genome of effector/memory CD4(+) T cells from MRL+/+ mice. Regardless of TCE exposure, 62% of CpG sites in autosomal chromosomes were hypomethylated (0-15% methylation), and 25% were hypermethylated (85-100% methylation)...
July 2017: Environmental Epigenetics
Beibei Wu, Liyin Wang, Lili Jiang, Lili Dong, Fengli Xu, Yili Lu, Jiahui Jin, Zhanyue Wang, Guang Liang, Xiaoou Shan
Neutrophils, immune cells crucial for protecting against invading pathogens, are important in sepsis. Neutrophil migration is regulated by chemokine receptors and their cognate ligands. Our previous study investigated the effect of n‑butanol extract from Folium isatidis on lipopolysaccharide (LPS)‑induced septic shock. The present study stimulated neutrophils with LPS to explore the influence of LPS on cell. Neutrophils were then pretreated with n‑butanol extract from Folium isatidis followed by LPS to examine the effect of this extract on neutrophil chemotaxis...
January 2018: Molecular Medicine Reports
Yong-Qiang Chen, Lu Zheng, Mohanad Aldarouish, Zhong-Hai Zhou, Ning Pan, Jun-Quan Liu, Fu-Xing Chen, Li-Xin Wang
γδT cells are a distinct T-cell subset that display unique characteristics regarding T-cell receptor gene usage, tissue tropism and antigen recognition. Adoptive γδT cell transfer therapy has recently been gaining importance as an efficient approach in cancer immunotherapy. However, exploiting γδT cell response for tumour immunotherapy is a challenge due to cell numbers, activities and differentiation states that minimize the clinical therapeutic effects. Previous studies have indicated that the wnt/β-catenin signalling pathway plays a crucial role in the differentiation, survival and enhancement of the immune response of T lymphocytes...
November 2, 2017: Experimental Cell Research
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