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Jiangao Zhu, Huiyao Chen, Xiaopei Huang, Songfu Jiang, Yiping Yang
Viral hepatitis remains a global health challenge despite recent progress in the development of more effective therapies. Although virus-specific CD8(+) and CD4(+) T cell responses are essential for viral clearance, it remains largely unknown what regulates T cell-mediated viral clearance. Thus, a better understanding of the regulation of anti-viral T cell immunity would be critical for the design of more effective therapies for viral hepatitis. Using a model of adenovirus-induced hepatitis, here we showed that adenoviral infection induced recruitment of Ly6C(hi) monocytes to the liver in a CCR2-dependent manner...
October 20, 2016: JCI Insight
Lisa R Young, Peter M Gulleman, Chelsi W Short, Harikrishna Tanjore, Taylor Sherrill, Aidong Qi, Andrew P McBride, Rinat Zaynagetdinov, John T Benjamin, William E Lawson, Sergey V Novitskiy, Timothy S Blackwell
Alveolar epithelial cell (AEC) dysfunction underlies the pathogenesis of pulmonary fibrosis in Hermansky-Pudlak syndrome (HPS) and other genetic syndromes associated with interstitial lung disease; however, mechanisms linking AEC dysfunction and fibrotic remodeling are incompletely understood. Since increased macrophage recruitment precedes pulmonary fibrosis in HPS, we investigated whether crosstalk between AECs and macrophages determines fibrotic susceptibility. We found that AECs from HPS mice produce excessive MCP-1, which was associated with increased macrophages in the lungs of unchallenged HPS mice...
October 20, 2016: JCI Insight
Damla Tokac, Erdem Tuzun, Huseyin Gulec, Vuslat Yılmaz, Elif Sinem Bireller, Bedia Cakmakoglu, Cem Ismail Kucukali
OBJECTIVE: Bipolar disorder (BD) is a debilitating psychiatric disease with unknown etiology. Recent studies have shown inflammation as a potential contributing factor of BD pathogenesis. However, potential associations between chemokine and chemokine receptor polymorphisms and BD have been fundamentally understudied. To identify participation of chemokines in BD pathogenesis, we examined genetic variants of several chemokine and chemokine receptor genes. METHODS: The study population comprised 200 patients with BD and 195 age- and sex-matched healthy controls...
September 2016: Psychiatry Investigation
Jie Qin, Yusuke Arakawa, Miwa Morita, John J Fung, Shiguang Qian, Lina Lu
BACKGROUND: Islet transplantation is a promising therapeutic approach for restore the physical response to blood glucose in type 1 diabetes. Current chronic use of immunosuppressive reagents for preventing islet allograft rejection is associated with severe complications. In addition, many of the immunosuppressive drugs are diabetogenic. The induction of transplant tolerance to eliminate the dependency on immunosuppression is ideal, but remains challenging. METHODS: Addition of hepatic stellate cells allowed generation of myeloid-derived suppressor cells (MDSC) from precursors in mouse bone marrow...
October 17, 2016: Transplantation
Jin-Jer Chen, Wen-Rui Hao, Kuan-Cheng Chang, Ju-Chi Liu
OBJECTIVE: Cardiac fibrosis is the major pathophysiological process, contributing to the development of diastolic heart failure. We examine the role of macrophage-derived galectin-3 (gal-3) in cardiac fibrosis and diastolic function in response to transverse aortic constriction (TAC). DESIGN AND METHOD: wild-type (WT) and gal-3 knock-out (KO) mice subjected to TAC; immunohistochemistry for myocardial macrophage infiltration,gal-3,and CTGF (connective tissue growth factor) expression; picrosirius red stain for myocardial fibrosis; FACS flow- cytometry for defining the origin of myocardial macrophages...
September 2016: Journal of Hypertension
Seungbum Kim, Gary Wang, Gilberto Lobaton, Eric Li, Tao Yang, Mohan Raizada
OBJECTIVE: Our previous studies have demonstrated that gut microbial dysbiosis is linked to high blood pressure in patients. This was associated with decreases in butyrate- and acetate- producing microbial populations. Thus, our objective in this study was to investigate the hypothesis that infusion of butyrate would impact dysbiosis, gut immunity and attenuate hypertension. DESIGN AND METHOD: C57B6 mice were divided into 4 groups; Saline infused, Angiotensin II (750ng/kg/min) infused, Ang II infused and butyrate treated (0...
September 2016: Journal of Hypertension
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
Bingjie Shi, Juan Li, Xuanling Shi, Wenxu Jia, Yi Wen, Xiongbing Hu, Fengfeng Zhuang, Jianzhong Xi, Linqi Zhang
Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity and low cytotoxicity. We report here systematic design and characterization of twenty eight novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity and lower cytotoxicity compared to zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials...
October 3, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
J Miotla Zarebska, A Chanalaris, C Driscoll, A Burleigh, R E Miller, A M Malfait, B Stott, T L Vincent
OBJECTIVE: The role of inflammation in structural and symptomatic osteoarthritis (OA) remains unclear. One key mediator of inflammation is the chemokine CCL2, primarily responsible for attracting monocytes to sites of injury. We investigated the role of CCL2 and its receptor CCR2 in experimental OA. DESIGN: OA was induced in 10 week old male wild type, Ccl2(-/-) and Ccr2(-/-) mice, by destabilisation of the medial meniscus (DMM). RNA was extracted from whole joints at 6h and 7 days post surgery and examined by RT-PCR...
October 13, 2016: Osteoarthritis and Cartilage
Kevin V Chow, Emma M Carrington, Yifan Zhan, Andrew M Lew, Robyn M Sutherland
Islet transplantation can cure type 1 diabetes, but is limited by lack of donor organs and early graft dysfunction, such that many patients require multiple transplants to achieve insulin independence. Monocyte derived dendritic cells (moDCs) arise during inflammation and allograft encounters where they can promote various innate and adaptive immune responses. To determine whether moDCs impair early graft function following allogeneic islet transplantation, we transplanted MHC-mismatched BALB/c (H-2d) islets into diabetic C57BL/6-CCR2...
October 13, 2016: Cell Transplantation
L F S Batista, Y T Utsunomiya, T B F da Silva, R A Dias, T Y Tomokane, A D Pacheco, V L R da Matta, F T Silveira, M Marcondes, C M Nunes, M D Laurenti
A genome-wide association study (GWAS) could unravel the complexity of the cell-mediated immunity (CMI) to canine leishmaniasis (CanL). Thereby we committed to scan 110,165 single-nucleotide polymorphisms (SNPs) aiming to identify chromosomal regions associated to leishmanin skin test (LST), lymphocyte proliferation assay (LPA) and cytokines responses to further understanding the role played by the CMI in the outcome of the natural Leishmania infantum infection in 189 dogs. Based on LST and LPA, four CMI profiles were identified (LST-/LPA-, LST+/LPA-, LST-/LPA+ and LST+/LPA+), which were not associated to subclinical infected or diseased dogs...
October 10, 2016: Infection and Immunity
Tobias Eggert, Katharina Wolter, Juling Ji, Chi Ma, Tetyana Yevsa, Sabrina Klotz, José Medina-Echeverz, Thomas Longerich, Marshonna Forgues, Florian Reisinger, Mathias Heikenwalder, Xin Wei Wang, Lars Zender, Tim F Greten
Oncogene-induced senescence causes hepatocytes to secrete cytokines, which induce their immune-mediated clearance to prevent tumor initiation, a process termed "senescence surveillance." However, senescent hepatocytes give rise to hepatocellular carcinomas (HCCs), if the senescence program is bypassed or if senescent cells are not cleared. Here, we show context-specific roles for CCR2(+) myeloid cells in liver cancer. Senescence surveillance requires the recruitment and maturation of CCR2(+) myeloid cells, and CCR2 ablation caused outgrowth of HCC...
October 10, 2016: Cancer Cell
Mary Francis, Richard Sun, Jessica A Cervelli, Hyejeong Choi, Mili Mandal, Elena V Abramova, Andrew J Gow, Jeffrey D Laskin, Debra L Laskin
Macrophages and inflammatory mediators have been implicated in ozone toxicity. In these studies, we used splenectomized (SPX) mice to assess the contribution of splenic monocytes to pulmonary inflammation and injury induced by ozone. Cells and tissue were collected 24-72 h after exposure of mice to air or ozone (0.8 ppm, 3 h). Following ozone exposure, increased numbers of pro-inflammatory CD11b(+)Ly6C(Hi) and anti-inflammatory CD11b(+)Ly6C(Lo) monocytes were observed in spleens of control (CTL) mice. CD11b(+)Ly6C(Hi) and MMP-9(+) pro-inflammatory macrophages were also observed in lungs of CTL mice after ozone, along with CD11b(+)Ly6C(Lo) and mannose receptor (MR)(+) anti-inflammatory macrophages...
October 5, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Katharine M Irvine, Xuan Banh, Victoria L Gadd, Kyle K Wojcik, Juliana K Ariffin, Sara Jose, Samuel Lukowski, Gregory J Baillie, Matthew J Sweet, Elizabeth E Powell
Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesizing that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage subpopulations. The proportion of CRIg(hi) macrophages differed between patients and in the same patient over time, and a high proportion of CRIg(hi) macrophages was associated with reduced disease severity (model for end-stage liver disease) score...
June 2, 2016: JCI Insight
Esin Aktas Cetin, Leyla Pur Ozyigit, Yusuf Metin Gelmez, Erkan Cakir, Ahmet Hakan Gedik, Gunnur Deniz
OBJECTIVES: Childhood tuberculosis (TB) comprises an important part of the world's TB burden. Monocytes set up the early phase of infection because of innate immune responses. Understanding the changes in monocyte subsets during multisystem infectious diseases may be important for the development of novel diagnostic and therapeutic strategies. The aim of this study was to evaluate the monocyte phenotype together with the cytokine secretion profiles of children with pulmonary tuberculosis...
September 29, 2016: Pediatric Pulmonology
Kae Won Cho, Brian F Zamarron, Lindsey A Muir, Kanakadurga Singer, Cara E Porsche, Jennifer B DelProposto, Lynn Geletka, Kevin A Meyer, Robert W O'Rourke, Carey N Lumeng
Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDCs), contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we use CD64 to distinguish ATM and ATDC, and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80(+)CD11b(+) cells overlaps with other leukocytes and that CD45(+)CD64(+) is specific for ATM...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Pierre-Louis Loyher, Juliette Rochefort, Camille Baudesson de Chanville, Pauline Hamon, Géraldine Lescaille, Chloé Bertolus, Maude Guillot-Delost, Matthew Krummel, Francois M Lemoine, Christophe Combadière, Alexandre Boissonnas
The CCL2 chemokine receptor CCR2 drives cancer by mediating recruitment of monocytes and myeloid-derived suppressor cells to the tumor microenvironment. In this study, we extend the significance of CCR2 in this setting by identifying a new role for it in mediating recruitment of CD4+ T regulatory cells (Treg). Following tumor initiation, an expanded population of CCR2+ Tregs required CCR2 expression to traffic between draining lymph nodes (dLN) and the tumor. This Treg subset was enriched in the fraction of tumor antigen-specific cells in the dLN, where they displayed an activated immunosuppressive phenotype...
September 28, 2016: Cancer Research
José L Reyes, Fernando Lopes, Gabriella Leung, Nicole L Mancini, Chelsea E Matisz, Arthur Wang, Emma A Thomson, Nicholas Graves, John Gilleard, Derek M McKay
Awareness of the immunological underpinnings of host-parasite interactions may reveal immune signaling pathways that could be used to treat inflammatory disease in humans. Previously we showed that infection with the rat tapeworm Hymenolepis diminuta, used as a model helminth, or systemic delivery of worm antigen (HdAg) significantly reduced the severity of dinitrobenzene sulphonic acid (DNBS)-induced colitis in mice. Extending these analyses, intraperitoneal injection of HdAg dose-dependently suppressed dextran sodium sulphate (DSS)-induced colitis and this was paralleled by reduced IFNγ, IL-17 and TNFα and increased IL-10 production from mitogen-activated splenocytes...
September 26, 2016: Infection and Immunity
Mu-En Lin, Theodore M Chen, Mary C Wallingford, Ngoc B Nguyen, Shunsuke Yamada, Chenphop Sawangmake, Jaimei Zhang, Mei Y Speer, Cecilia M Giachelli
AIMS: Vascular smooth muscle cells (SMCs) are major precursors contributing to osteochondrogenesis and calcification in atherosclerosis. Runt-related transcription factor-2 (Runx2) has been found essential for SMC differentiation to an osteochondrogenic phenotype and subsequent calcification in vitro A recent study using a conditional targeting allele that produced a truncated Runx2 protein in SMCs of ApoE(-/-) mice showed reduced vascular calcification, likely occurring via reduction of receptor activator of nuclear factor-κB ligand (RANKL), macrophage infiltration, and atherosclerotic lesion formation...
September 26, 2016: Cardiovascular Research
Anne M Fitzpatrick, Susan T Stephenson, Milton R Brown, Khristopher Nguyen, Shaneka Douglas, Lou Ann S Brown
BACKGROUND: Severe asthma in children is a heterogeneous disorder associated with variable responses to corticosteroid treatment. Criterion standards for corticosteroid responsiveness assessment in children are lacking. OBJECTIVE: This study sought to characterize systemic corticosteroid responses in children with severe asthma after treatment with intramuscular triamcinolone and to identify phenotypic and molecular predictors of an intramuscular triamcinolone response...
September 21, 2016: Journal of Allergy and Clinical Immunology in Practice
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