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https://www.readbyqxmd.com/read/28799208/ccr2-monocytic-myeloid-derived-immunosuppressive-cells-m-mdsc-inhibit-collagen-degradation-and-promote-lung-fibrosis-by-producing-tgf-%C3%AE-1
#1
Astrid Lebrun, Sandra Lo Re, Mathilde Chantry, Xavier Izquierdo Carerra, Francine Uwambayinema, Doriana Ricci, Raynal Devosse, Saloua Ibouraadaten, Lisa Brombin, Mihaly Palmai-Pallag, Yousof Yakoub, Manolis Pasparakis, Dominique Lison, François Huaux
Monocytes infiltrating scar tissue are predominantly viewed as progenitor cells. Here, we show that tissue CCR2(+) monocytes possess specific immunosuppressive and pro-fibrotic functions. CCR2(+) monocytic cells are acutely recruited to the lung before the onset of silica-induced fibrosis in mice. These tissue monocytes are defined as monocytic-Myeloid-Derived Suppressor Cells (M-MDSC) because they significantly suppress T lymphocyte proliferation in vitro. M-MDSC collected from silica-treated mice also express TGF-β1, which stimulates lung fibroblasts to release TIMP-1, an inhibitor of metalloproteinase collagenolytic activity...
August 11, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28798369/inflammatory-role-of-dendritic-cells-in-amyotrophic-lateral-sclerosis-revealed-by-an-analysis-of-patients-peripheral-blood
#2
Michela Rusconi, Francesca Gerardi, William Santus, Andrea Lizio, Valeria Ada Sansone, Christian Lunetta, Ivan Zanoni, Francesca Granucci
Chronic inflammation is one of the causes of neurodegeneration in Amyotrophic lateral sclerosis (ALS). Here we examined whether circulating dendritic cells (DCs) can contribute to disease progression. We found ALS patients show a significant reduction in the number of circulating DCs. Also, patients' DCs present an increased expression of CD62L and a tendency to overexpress CCR2 compared with healthy donors. Moreover, DCs derived from a subpopulation of ALS patients produced higher levels of IL-8 and CCL-2 upon lipopolysaccharide (LPS)-stimulation...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28794879/human-papillomavirus-driven-immune-deviation-challenge-and-novel-opportunity-for-immunotherapy
#3
REVIEW
Sigrun Smola, Connie Trimble, Peter L Stern
It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer...
June 2017: Therapeutic Advances in Vaccines
https://www.readbyqxmd.com/read/28783667/tumor-location-determines-tissue-specific-recruitment-of-tumor-associated-macrophages-and-antibody-dependent-immunotherapy-response
#4
Birgit Lehmann, Markus Biburger, Christin Brückner, Andrea Ipsen-Escobedo, Sina Gordan, Christian Lehmann, David Voehringer, Thomas Winkler, Niels Schaft, Diana Dudziak, Horia Sirbu, Georg F Weber, Falk Nimmerjahn
Despite recent advances in activating immune cells to target tumors, the presence of some immune cells, such as tumor-associated macrophages (TAMs) or tumor-associated neutrophils (TANs), may promote rather than inhibit tumor growth. However, it remains unclear how antibody-dependent tumor immunotherapies, such as cytotoxic or checkpoint control antibodies, affect different TAM or TAN populations, which abundantly express activating Fcγ receptors. In this study, we show that the tissue environment determines which cellular effector pathways are responsible for antibody-dependent tumor immunotherapy...
January 6, 2017: Science Immunology
https://www.readbyqxmd.com/read/28780502/pulmonary-ccr2-cd4-t-cells-are-immune-regulatory-and-attenuate-lung-fibrosis-development
#5
Katrin Milger, Yingyan Yu, Eva Brudy, Martin Irmler, Alla Skapenko, Michael Mayinger, Mareike Lehmann, Johannes Beckers, Frank Reichenberger, Jürgen Behr, Oliver Eickelberg, Melanie Königshoff, Susanne Krauss-Etschmann
BACKGROUND: Animal models have suggested that CCR2-dependent signalling contributes to the pathogenesis of pulmonary fibrosis, but global blockade of CCL2 failed to improve the clinical course of patients with lung fibrosis. However, as levels of CCR2(+)CD4(+) T cells in paediatric lung fibrosis had previously been found to be increased, correlating with clinical symptoms, we hypothesised that distinct CCR2(+) cell populations might either increase or decrease disease pathogenesis depending on their subtype...
August 5, 2017: Thorax
https://www.readbyqxmd.com/read/28780056/chemokine-ligand-2-chemokine-receptor-2-signaling-in-the-trigeminal-ganglia-contributes-to-inflammatory-hyperalgesia-in-rats
#6
Mamoru Takeda, Masanori Nasu, Takuya Kanazawa, Masayuki Takahashi, Yoshihito Shimazu
This study investigated the functional significance of hyperalgesia in the CCL2/CCR2 signaling system in trigeminal ganglion (TG) neurons following inflammation. Inflammation was induced by injection of complete Freund's adjuvant (CFA) into the whisker pad of rats. The escape threshold from mechanical stimulation applied to the whisker pad 2days later was significantly lower in CFA-treated rats than in naïve rats. Fluorogold (FG) labeling was used to identify the TG neurons innervating the whisker pad. FG-labeled TG neurons were immunoreactive for CCL2/CCR2...
August 2, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28768911/a-ccr2-myeloid-cell-niche-required-for-pancreatic-%C3%AE-cell-growth
#7
Kristin Mussar, Stephanie Pardike, Tobias M Hohl, Gary Hardiman, Vincenzo Cirulli, Laura Crisa
Organ-specific patterns of myeloid cells may contribute tissue-specific growth and/or regenerative potentials. The perinatal stage of pancreas development marks a time characterized by maximal proliferation of pancreatic islets, ensuring the maintenance of glucose homeostasis throughout life. Ontogenically distinct CX3CR1+ and CCR2+ macrophage populations have been reported in the adult pancreas, but their functional contribution to islet cell growth at birth remains unknown. Here, we uncovered a temporally restricted requirement for CCR2+ myeloid cells in the perinatal proliferation of the endocrine pancreatic epithelium...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28763796/the-metabolic-regulator-mtorc1-controls-terminal-myeloid-differentiation
#8
Pui Y Lee, David B Sykes, Sarah Ameri, Demetrios Kalaitzidis, Julia F Charles, Nathan Nelson-Maney, Kevin Wei, Pierre Cunin, Allyn Morris, Astrid E Cardona, David E Root, David T Scadden, Peter A Nigrovic
Monocytes are derived from hematopoietic stem cells through a series of intermediate progenitor stages, but the factors that regulate this process are incompletely defined. Using a Ccr2/Cx3cr1 dual-reporter system to model murine monocyte ontogeny, we conducted a small-molecule screen that identified an essential role of mechanistic target of rapamycin complex 1 (mTORC1) in the development of monocytes and other myeloid cells. Confirmatory studies using mice with inducible deletion of the mTORC1 component Raptor demonstrated absence of mature circulating monocytes, as well as disruption in neutrophil and dendritic cell development, reflecting arrest of terminal differentiation at the granulocyte-monocyte progenitor stage...
May 26, 2017: Science Immunology
https://www.readbyqxmd.com/read/28762187/the-choroid-plexus-is-a-key-cerebral-invasion-route-for-t-cells-after-stroke
#9
Gemma Llovera, Corinne Benakis, Gaby Enzmann, Ruiyao Cai, Thomas Arzberger, Alireza Ghasemigharagoz, Xiang Mao, Rainer Malik, Ivana Lazarevic, Sabine Liebscher, Ali Ertürk, Lilja Meissner, Denis Vivien, Christof Haffner, Nikolaus Plesnila, Joan Montaner, Britta Engelhardt, Arthur Liesz
Neuroinflammation contributes substantially to stroke pathophysiology. Cerebral invasion of peripheral leukocytes-particularly T cells-has been shown to be a key event promoting inflammatory tissue damage after stroke. While previous research has focused on the vascular invasion of T cells into the ischemic brain, the choroid plexus (ChP) as an alternative cerebral T-cell invasion route after stroke has not been investigated. We here report specific accumulation of T cells in the peri-infarct cortex and detection of T cells as the predominant population in the ipsilateral ChP in mice as well as in human post-stroke autopsy samples...
July 31, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28761107/regulatory-t-cells-from-pancreatic-lymphnodes-of-patients-with-type-1-diabetes-express-increased-levels-of-microrna-mir-125a-5p-that-limits-ccr2-expression
#10
Guido Sebastiani, Giuliana Ventriglia, Angela Stabilini, Carlo Socci, Cristina Morsiani, Andrea Laurenzi, Laura Nigi, Caterina Formichi, Bechara Mfarrej, Alessandra Petrelli, Georgia Fousteri, Todd M Brusko, Francesco Dotta, Manuela Battaglia
Autoimmune type 1 diabetes (T1D) is thought to be caused by a defective immune regulation with regulatory T (Treg) cells playing a fundamental role in this process. Tolerance mechanisms depend on tunable responses that are sensitive to minor perturbations in the expression of molecules that can be carried out by multiple epigenetic mechanisms, including regulation by microRNAs. In this study, microRNA expression profile was investigated in Treg cells isolated from peripheral blood (PB) and from pancreatic draining lymph nodes (PLN) of T1D patients and non-diabetic subjects...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28754304/a-natural-ccr2-antagonist-relieves-tumor-associated-macrophage-mediated-immunosuppression-to-produce-a-therapeutic-effect-for-liver-cancer
#11
Wenbo Yao, Qian Ba, Xiaoguang Li, Huiliang Li, Shoude Zhang, Ya Yuan, Feng Wang, Xiaohua Duan, Jingquan Li, Weidong Zhang, Hui Wang
Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28749716/predilection-to-dermato-lymphangio-adenitis-in-obstructive-lymphedema-of-lower-limbs-depending-on-genetic-polymorphisms-at-tnf%C3%AE-308g-a-ccr2-190g-a-cd14-159c-t-tlr2-2029c-t-tlr4-1063a-g-tlr4-1363c-t-tgf%C3%AE-74g-c-and-tgf%C3%AE-29t-c
#12
Waldemar L Olszewski, Malgorzata Zagozda, Marzanna T Zaleska, Marek Durlik
BACKGROUND: Infection is the most common type of complication observed in lymphedema and is promoted by lymphatic system dysfunction, which causes locoregional immune disorders. Infectious complications are primarily bacterial and most commonly cellulitis (dermato-lymphangio-adenitis, DLA) caused by patients' own skin Staphylococci epidermidis and aureus. The clinical course and outcomes in the immune response to infection have been shown to be associated with genetic polymorphisms. AIM: To investigate polymorphism of TNFα-308G>A, CCR2-190G>A, CD14-159C>T, TLR2 2029C>T, TLR4 1063A>G, TLR4 1363C>T, TGFβ 74G>C, and TGFβ 29T>C...
July 27, 2017: Lymphatic Research and Biology
https://www.readbyqxmd.com/read/28748061/host-molecular-factors-and-viral-genotypes-in-the-mother-to-child-hiv-1-transmission-in-sub-saharan-africa
#13
REVIEW
Linda Chapdeleine M Mouafo, Béatrice Dambaya, Nicole N Ngoufack, Céline N Nkenfou
Maternal viral load and immune status, timing and route of delivery, viral subtype, and host genetics are known to influence the transmission, acquisition and disease progression of human immunodeficiency virus-1 (HIV-1) infection. This review summarizes the findings from published works on host molecular factors and virus genotypes affecting mother to child transmission (MTCT) in Africa and identifies the gaps that need to be addressed in future research. Articles in PubMed, Google and AIDSearch and relevant conference abstracts publications were searched...
June 23, 2017: Journal of Public Health in Africa
https://www.readbyqxmd.com/read/28747747/involvement-of-monocyte-subsets-in-the-immunopathology-of-giant-cell-arteritis
#14
Yannick van Sleen, Qi Wang, Kornelis S M van der Geest, Johanna Westra, Wayel H Abdulahad, Peter Heeringa, Annemieke M H Boots, Elisabeth Brouwer
Monocytes/macrophages are critical in systemic and local inflammation in giant cell arteritis (GCA) and possibly in clinically overlapping polymyalgia rheumatica (PMR). Therefore, we aimed to understand the contribution of monocyte subsets and the CX3CR1-CX3CL1 and CCR2-CCL2 migratory pathways, to the pathology of GCA. Peripheral blood monocytes were enumerated in samples from newly-diagnosed, untreated GCA and PMR patients and after prednisone-induced remission. The distribution of classical (CD14(bright)CD16(neg)) and the more pro-inflammatory, intermediate (CD14(bright)CD16+) and non-classical (CD14(dim)CD16+) monocyte subsets was analysed by flow cytometry...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746827/monocyte-depletion-early-after-stroke-promotes-neurogenesis-from-endogenous-neural-stem-cells-in-adult-brain
#15
Cecilia Laterza, Somsak Wattananit, Naomi Uoshima, Ruimin Ge, Daniel Tornero, Emanuela Monni, Olle Lindvall, Zaal Kokaia
Ischemic stroke, caused by middle cerebral artery occlusion, leads to long-lasting formation of new striatal neurons from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) of adult rodents. Concomitantly with this neurogenic response, SVZ exhibits activation of resident microglia and infiltrating monocytes. Here we show that depletion of circulating monocytes, using the anti-CCR2 antibody MC-21 during the first week after stroke, enhances striatal neurogenesis at one week post-insult, most likely by increasing short-term survival of the newly formed neuroblasts in the SVZ and adjacent striatum...
July 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28736230/pro-inflammatory-chemokines-and-cytokines-dominate-the-blister-fluid-molecular-signature-in-epidermolysis-bullosa-patients-and-affect-leukocyte-and-stem-cell-migration
#16
Vitali Alexeev, Julio Cesar Salas-Alanis, Francis Palisson, Lila Mukhtarzada, Giulio Fortuna, Jouni Uitto, Andy South, Olga Igoucheva
Hereditary epidermolysis bullosa (EB) is associated with skin blistering and the development of chronic non-healing wounds. Although clinical studies have shown that cell-based therapies improve wound healing, recruitment of therapeutic cells to blistering skin and to more advanced skin lesions remains a challenge. Here, we analyzed cytokines and chemokines in blister fluids (BF) of patients affected by dystrophic, junctional and simplex EB. Our analysis revealed high levels of CXCR1, CXCR2, CCR2 and CCR4 ligands, particularly dominant in dystrophic and junctional EB...
July 20, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28730964/ccl2-is-modulated-by-cytokines-and-ppar-g-in-anaplastic-thyroid-cancer
#17
Silvia Martina Ferrari, Giusy Elia, Simona Piaggi, Enke Baldini, Salvatore Ulisse, Mario Miccoli, Gabriele Materazzi, Alessandro Antonelli, Poupak Fallahi
BACKGROUND AND OBJECTIVE: Chemokine (C-C motif) ligand (CCL)2, the prototype Th2 chemokine, is secreted by tumor cells, and has growth promoting effects. Whether CCL2 protumorigenic activities will be validated, then CCL2 and its receptor CCR2 may be therapeutic targets in cancer. METHODS: We tested in "primary human anaplastic thyroid carcinoma (ATC) cells" (ANA) versus "normal thyroid follicular cells" (TFC): a) CCL2 secretion basally, after IFN-g and/or TNF-a stimulation; b) PPARg activation by thiazolidinediones (TZDs), rosiglitazone or pioglitazone, on CCL2 secretion, and on proliferation and apoptosis in ANA...
July 19, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28722019/sustained-accumulation-of-antigen-presenting-cells-after-infection-promotes-local-t-cell-immunity
#18
Nicholas Collins, Katharina Hochheiser, Francis R Carbone, Thomas Gebhardt
Antigen-presenting cells (APC) such as dendritic cells (DC) and macrophages are critical for T cell-mediated immunity. While it is established that memory T cells accumulate and persist in peripheral tissues after the resolution of infection, whether this is also the case for APC remains unclear. Here, we report that CCR2-dependent cells infiltrate skin during acute infection with herpes simplex virus (HSV)-1 and subsequently give rise to localized populations of dendritic cells and macrophages. These APC are found at elevated numbers at sites of resolved infection or inflammation compared to unaffected regions of skin...
July 19, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28716963/chemokine-ccl2-ccr2-signaling-induces-neuronal-cell-death-via-stat3-activation-and-il-1%C3%AE-production-after-status-epilepticus
#19
Dai-Shi Tian, Jiyun Peng, Madhuvika Murugan, Lijie Feng, Jun-Li Liu, Ukpong B Eyo, Li-Jun Zhou, Rochelle Mogilevsky, Wei Wang, Long-Jun Wu
Elevated levels of chemokine C-C motif ligand 2 (CCL2) and its receptor CCR2 have been reported in patients with temporal lobe epilepsy and in experimental seizures. However, the functional significance and molecular mechanism underlying CCL2-CCR2 signaling in epileptic brain remains largely unknown. In this study, we found that the upregulated CCL2 was mainly expressed in hippocampal neurons and activated microglia from mice 1d after kainic acid (KA)-induced seizures. Taking advantage of CX3CR1(GFP/+):CCR2(RFP/+) double transgenic mice, we demonstrated that CCL2-CCR2 signaling participated in resident microglial activation and blood-derived monocyte infiltration...
July 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28716525/peri-tumor-associated-fibroblasts-promote-intrahepatic-metastasis-of-hepatocellular-carcinoma-by-recruiting-cancer-stem-cells
#20
Jinghua Jiang, Fei Ye, Xue Yang, Chen Zong, Lu Gao, Yang Yang, Qiudong Zhao, Zhipeng Han, Lixin Wei
Fibroblasts have been reported to play an important role in hepatocellular carcinoma (HCC). However, the role of fibroblasts have not been fully understood. Conditioned medium collected from human peri-tumor tissue-derived fibroblasts (CM-pTAFs) showed high metastasis ability than human HCC tissues-derived fibroblasts (CM-TAFs). To determine what component was secreted from fibroblasts, we used Bio-Plex analysis system and compared the factors secreted from CM-pTAFs and CM-TAFs, found a series of up-regulated cytokines in the CM-pTAFs, including IL-6, CCL2, CXCL1, CXCL8, SCGF-β, HGF and VEGF...
July 15, 2017: Cancer Letters
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