Search results for "CCR"
showing 10 items of 574 documents
Sr isotope variations in the Upper Triassic succession at Pizzo Mondello, Sicily: Constraints on the timing of the Cimmerian Orogeny
2018
Abstract The Late Triassic Cimmerian Orogeny was a result of the final closure of the Palaeotethys Ocean and the accretion of Gondwana-derived (Cimmerian) continents to southern Eurasia. Determining the timing of the Cimmerian Orogeny is crucial to our understanding of the large-scale climate changes driven by the uplift of the Cimmerian Mountains. Here we present stratigraphic variations in 87Sr/86Sr values of Upper Triassic pelagic limestone from the Pizzo Mondello section, Sicily, Italy, that constrain the timing of uplift of the Cimmerian Mountains. The 87Sr/86Sr values remain relatively constant in the lower part of the section, decreasing slightly in the Tuvalian (upper Carnian) and L…
Multiple paths to cold tolerance: the role of environmental cues, morphological traits and the circadian clock gene vrille
2021
AbstractBackgroundTracing the association between insect cold tolerance and latitudinally and locally varying environmental conditions, as well as key morphological traits and molecular mechanisms, is essential for understanding the processes involved in adaptation. We explored these issues in two closely-related species, Drosophila montana and Drosophila flavomontana, originating from diverse climatic locations across several latitudes on the coastal and mountainous regions of North America. We also investigated the association between sequence variation in one of the key circadian clock genes, vrille, and cold tolerance in both species. Finally, we studied the impact of vrille on fly cold…
Cold adaptation drives population genomic divergence in the ecological specialist, Drosophila montana
2020
Funding: UK Natural Environment Research Council (Grant Number(s): NE/L501852/1, NE/P000592/1); Academy of Finland (GrantNumber(s): 267244, 268214, 322980), Ella ja Georg Ehrnroothin Säätiö. Detecting signatures of ecological adaptation in comparative genomics is challenging, but analysing population samples with characterised geographic distributions, such as clinal variation, can help identify genes showing covariation with important ecological variation. Here, we analysed patterns of geographic variation in the cold-adapted species Drosophila montana across phenotypes, genotypes and environmental conditions and tested for signatures of cold adaptation in population genomic divergence. We…
Human ectonucleotidase-expressing CD25 high Th17 cells accumulate in breast cancer tumors and exert immunosuppressive functions
2015
IF 7.644; International audience; Th17 cells contribute to the development of some autoimmune and allergic diseases by driving tissue inflammation. However, the function of Th17 cells during cancer progression remains controversial. Here, we show that human memory CD25(high) Th17 cells suppress T cell immunity in breast cancer. Ectonucleotidase-expressing Th17 cells accumulated in breast cancer tumors and suppressed CD4(+) and CD8(+) T cell activation. These cells expressed both Ror gamma t and Foxp3 genes and secreted Th17 related cytokines. We further found that CD39 ectonucleotisase expression on tumor-infiltrating Th17 cells was driven by TGF-beta and IL-6. Finally, immunohistochemical …
Disruption of the CCL1-CCR8 axis inhibits vascular Treg recruitment and function and promotes atherosclerosis in mice
2019
The CC chemokine 1 (CCL1, also called I-309 or TCA3) is a potent chemoattractant for leukocytes that plays an important role in inflammatory processes and diseases through binding to its receptor CCR8. Here, we investigated the role of the CCL1-CCR8 axis in atherosclerosis. We found increased expression of CCL1 in the aortas of atherosclerosis-prone fat-fed apolipoprotein E (Apoe)-null mice; moreover, in vitro flow chamber assays and in vivo intravital microscopy demonstrated an essential role for CCL1 in leukocyte recruitment. Mice doubly deficient for CCL1 and Apoe exhibited enhanced atherosclerosis in aorta, which was associated with reduced plasma levels of the anti-inflammatory interle…
The role of tumor-associated macrophages in gastric cancer development and their potential as a therapeutic target.
2020
Gastric cancer (GC) represents the fifth cause of cancer-related death worldwide. Molecular biology has become a central area of research in GC and there are currently at least three major classifications available to elucidate the mechanisms that drive GC oncogenesis. Further, tumor microenvironment seems to play a crucial role, and tumor-associated macrophages (TAMs) are emerging as key players in GC development. TAMs are cells derived from circulating chemokine- receptor-type 2 (CCR2) inflammatory monocytes in blood and can be divided into two main types, M1 and M2 TAMs. M2 TAMs play an important role in tumor progression, promoting a pro-angiogenic and immunosuppressive signal in the tu…
Intervention of Inflammatory Monocyte Activity Limits Dermal Fibrosis
2019
Monocytes and monocyte-derived cells are important players in the initiation, progression, and resolution of inflammatory skin reactions. As inflammation is a prerequisite for fibrosis development, we focused on the role of monocytes in cutaneous fibrosis, the clinical hallmark of patients suffering from systemic sclerosis. Investigating the function of monocytes in reactive oxygen species–induced dermal fibrosis, we observed that early monocyte depletion partially reduced disease severity. Low numbers of inflammatory Ly6Chigh monocytes, as well as inhibition of CCR2 and CCL2 in wild type animals by a specific L-RNA aptamer, mitigated disease parameters, indicating a pivotal role for CCR2+ …
NFATc1 releases BCL6-dependent repression of CCR2 agonist expression in peritoneal macrophages fromSaccharomyces cerevisiaeinfected mice
2016
The link between the extensive usage of calcineurin (CN) inhibitors cyclosporin A and tacrolimus (FK506) in transplantation medicine and the increasing rate of opportunistic infections within this segment of patients is alarming. Currently, how peritoneal infections are favored by these drugs, which impair the activity of several signaling pathways including the Ca(++) /CN/NFAT, Ca(++) /CN/cofilin, Ca(++) /CN/BAD, and NF-κB networks, is unknown. Here, we show that Saccharomyces cerevisiae infection of peritoneal resident macrophages triggers the transient nuclear translocation of NFATc1β isoforms, resulting in a coordinated, CN-dependent induction of the Ccl2, Ccl7, and Ccl12 genes, all enc…
IL-10-Modulated Human Dendritic Cells for Clinical Use: Identification of a Stable and Migratory Subset with Improved Tolerogenic Activity.
2015
Abstract Dendritic cells (DCs) are key regulators of protective immune responses and tolerance to (self-)Ags. Therefore, the scientific rationale for the use of tolerogenic DC therapy in the fields of allergies, autoimmunity, and transplantation medicine is strong. In this study, we analyzed the tolerogenic capacity of IL-10–modulated DC (IL-10DC) subpopulations to identify a DC subset that combines potent immunosuppressive activities with valuable immune properties for clinical implementation. IL-10DCs consist of two phenotypically distinct subpopulations: CD83highCCR7+ IL-10DCs and CD83lowCCR7− IL-10DCs. Suppressor assays with activated effector T cells revealed that CD4+ regulatory T cel…
Eosinophil depletion suppresses radiation-induced small intestinal fibrosis.
2017
Radiation-induced intestinal fibrosis (RIF) is a serious complication after abdominal radiotherapy for pelvic tumor or peritoneal metastasis. Herein, we show that RIF is mediated by eosinophil interactions with α-smooth muscle actin-positive (α-SMA+) stromal cells. Abdominal irradiation caused RIF especially in the submucosa (SM) of the small intestine, which was associated with the excessive accumulation of eosinophils in both human and mouse. Eosinophil-deficient mice showed markedly ameliorated RIF, suggesting the importance of eosinophils. After abdominal irradiation, chronic crypt cell death caused elevation of extracellular adenosine triphosphate, which in turn activated expression of…