Abstract:
:Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL) cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6R agonist uridine-5'-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Müller T,Fay S,Vieira RP,Karmouty-Quintana H,Cicko S,Ayata CK,Zissel G,Goldmann T,Lungarella G,Ferrari D,Di Virgilio F,Robaye B,Boeynaems JM,Lazarowski ER,Blackburn MR,Idzko Mdoi
10.3389/fimmu.2017.01028subject
Has Abstractpub_date
2017-08-22 00:00:00pages
1028issn
1664-3224journal_volume
8pub_type
杂志文章abstract::Behavioral comorbidities (depression, anxiety, fatigue, cognitive disturbances, and neuropathic pain) are prevalent in cancer patients and survivors. These mental and neurological health issues reduce quality-of-life, which is a significant societal concern given the increasing rates of long-term survival after variou...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01195
更新日期:2018-06-07 00:00:00
abstract::CD83 is a member of the immunoglobulin (Ig) superfamily and is expressed in membrane bound or soluble forms. Membrane CD83 (mCD83) can be detected on a variety of activated immune cells, although it is most highly and stably expressed by mature dendritic cells (DC). mCD83 regulates maturation, activation and homeostas...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01312
更新日期:2019-06-07 00:00:00
abstract::Effective immunity requires that a limited TCR repertoire is able to recognize a vast number of foreign peptide-MHCI (peptide-major histocompatibility complex class I) molecules. This challenge is overcome by the ability of individual TCRs to recognize large numbers of peptides. Recently, it was demonstrated that MHCI...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00199
更新日期:2013-07-23 00:00:00
abstract::Hyaluronan (HA), the major extracellular matrix component, is often anchored to CD44, a family of structurally/functionally important cell surface receptors. Recent results indicate that UV irradiation (UVR)-induced cutaneous squamous cell carcinomas (SCC) overexpress a variety of CD44 variant isoforms (CD44v), with d...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00224
更新日期:2015-05-13 00:00:00
abstract::Bruton's tyrosine kinase (Btk) is a signaling molecule involved in development and activation of B cells through B-cell receptor (BCR) and Toll-like receptor (TLR) signaling. We have previously shown that transgenic mice that overexpress human Btk under the control of the CD19 promoter (CD19-hBtk) display spontaneous ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00095
更新日期:2019-01-30 00:00:00
abstract::Trauma represents a major socioeconomic burden worldwide. After a severe injury, hemorrhagic shock (HS) as a frequent concomitant aspect is a central driver of systemic inflammation and organ damage. The kidney is often strongly affected by traumatic-HS, and acute kidney injury (AKI) poses the patient at great risk fo...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.02081
更新日期:2020-08-26 00:00:00
abstract::Monocytes and macrophages play pivotal roles in inflammation and homeostasis. Recent studies suggest that dynamic programing of macrophages and monocytes may give rise to distinct "memory" states. Lipopolysaccharide (LPS), a classical pattern recognition molecule, dynamically programs innate immune responses. Emerging...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00680
更新日期:2015-01-06 00:00:00
abstract::B-cell expansion with NF-κB and T-cell anergy (BENTA) disease is a B-cell-specific lymphoproliferative disorder caused by germline gain-of-function mutations in CARD11. These mutations force the CARD11 scaffold into an open conformation capable of stimulating constitutive NF-κB activation in lymphocytes, without requi...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.00198
更新日期:2018-02-08 00:00:00
abstract::Rationale: Caspase-1 is a zymogen whose activation predominantly depends upon the assembly of ASC monomers into insoluble prion-like polymers (specks). ASC polymers support caspase-1 dimer formation inducing a proximity mediated auto-activation of caspase-1. Therefore, the amount and nature of ASC monomers and polymer...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00461
更新日期:2020-03-19 00:00:00
abstract::Background: Each year, over 5 million red blood cell (RBC) transfusions are administered to patients in the USA. Despite the therapeutic benefits of RBC transfusions, there are associated risks. RBC-specific alloantibodies may form in response to antigenic differences between RBC donors and recipients; these alloantib...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02200
更新日期:2018-10-05 00:00:00
abstract::Depression is considered a neuropsychiatric disease associated with various neuronal changes within specific brain regions. We previously reported that ginsenoside-Rg1, a potential neuroprotective agent extracted from ginseng, significantly alleviated depressive-like disorders induced by chronic stress in rats. Howeve...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02889
更新日期:2018-12-07 00:00:00
abstract::Intravenous IgG (IVIg) contains polyclonal immunoglobulin G (IgG) from thousands of donors. It is administered at a low dose at regular intervals as antibody replacement therapy and at a higher dose as immunomodulatory treatment in various auto-immune or auto-inflammatory diseases. The working mechanism of immunomodul...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00674
更新日期:2015-01-21 00:00:00
abstract::Vaccination with CD1d-binding glycolipid adjuvants and co-administered protein, lipid, and carbohydrate antigens leads to invariant natural killer T (NKT) cell-dependent enhancement of protective B cell responses. NKT cell activation boosts the establishment of protein antigen-specific B cell memory and long-lived pla...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.00305
更新日期:2018-02-22 00:00:00
abstract::Antibody deficiency or hypogammaglobulinemia can have primary or secondary etiologies. Primary antibody deficiency (PAD) is the result of intrinsic genetic defects, whereas secondary antibody deficiency may arise as a consequence of underlying conditions or medication use. On a global level, malnutrition, HIV, and mal...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00033
更新日期:2019-02-08 00:00:00
abstract::The complement system is a key component of innate immunity which readily responds to invading microorganisms. Activation of the complement system typically occurs via three main pathways and can induce various antimicrobial effects, including: neutralization of pathogens, regulation of inflammatory responses, promoti...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01450
更新日期:2020-07-09 00:00:00
abstract::The innate immune system plays a critical early role in host defense against viruses, bacteria, and tumor cells. Until recently, natural killer (NK) cells and lymphoid tissue inducer (LTi) cells were the primary members of the innate lymphocyte family: NK cells form the front-line interface between the external enviro...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00022
更新日期:2013-03-04 00:00:00
abstract::Allograft rejection constitutes a major complication of solid organ transplantation requiring prophylactic/therapeutic immunosuppression, which increases susceptibility of patients to infections and cancer. Beyond the pivotal role of alloantigen-specific T cells and antibodies in the pathogenesis of rejection, natural...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00166
更新日期:2017-02-16 00:00:00
abstract::Therapeutic monoclonal antibodies (mAbs), targeting tumor antigens, or immune checkpoints, have demonstrated a remarkable anti-tumor effect against various malignancies. However, high costs for mono- or combination therapies, associated with adverse effects or possible development of resistance in some patients, warra...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00895
更新日期:2020-05-27 00:00:00
abstract::An important goal for personalized treatment is predicting response to a particular therapeutic. A drawback of biological treatment is immunogenicity and the development of antibodies directed against the drug [anti-drug antibodies (ADA)], which are associated with a poorer clinical outcome. Here we set out to identif...
journal_title:Frontiers in immunology
pub_type: 杂志文章,多中心研究
doi:10.3389/fimmu.2018.02865
更新日期:2018-12-05 00:00:00
abstract::Fungal bioaerosols are ubiquitous in the environment and human exposure can result in a variety of health effects ranging from systemic, subcutaneous, and cutaneous infections to respiratory morbidity including allergy, asthma, and hypersensitivity pneumonitis. Recent research has focused on the role of microRNAs (miR...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.00170
更新日期:2018-02-07 00:00:00
abstract::Neutrophil extracellular traps (NETs) are chromatin filaments decorated with enzymes from neutrophil cytoplasmic granules. Anti-neutrophil cytoplasmic antibodies (ANCAs) bind to enzymes from neutrophil cytoplasmic granules and are biomarkers for the diagnosis of systemic vasculitides. ANCA diagnostics are based on ind...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00439
更新日期:2017-04-13 00:00:00
abstract::Damage associated molecular patterns (DAMPs) are endogenous molecules originate from damaged cells and tissues with the ability to trigger and/or modify innate immune responses. Upon hemolysis hemoglobin (Hb) is released from red blood cells (RBCs) to the circulation and give a rise to the production of different Hb r...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2020.01323
更新日期:2020-06-30 00:00:00
abstract::High-throughput sequencing has the power to reveal the nature of adaptive immunity as represented by the full complexity of T-cell receptor (TCR) and antibody (IG) repertoires, but is at present severely compromised by the quantitative bias, bottlenecks, and accumulated errors that inevitably occur in the course of li...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00456
更新日期:2013-12-23 00:00:00
abstract::Amino acids (AAs) are necessary nutrients which act not only as building blocks in protein synthesis but also in crucial anabolic cellular signaling pathways. It has been demonstrated that SLC7A5 is a critical transporter that mediates uptake of several essential amino acids in highly proliferative tumors and activate...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00053
更新日期:2018-01-25 00:00:00
abstract::The developmental origin of allergic diseases has been suggested, but the molecular basis remains enigmatic. Exposure to environmental factors, such as di-(2-ethylhexyl) phthalate (DEHP; a common plasticizer), is suggested to be associated with increased childhood allergic asthma, but the causal relationship and its u...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.603831
更新日期:2020-12-23 00:00:00
abstract::Laboratory of genetics and physiology 2 (LGP2) is a key component of RIG-I-like receptors (RLRs). However, the lack of the caspase recruitment domains (CARDs) results in its controversial functional performance as a negative or positive regulator in antiviral responses. Especially, no sufficient evidence uncovers the ...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00352
更新日期:2017-03-27 00:00:00
abstract::Mast cells are immune cells of the myeloid lineage and are present in connective tissues throughout the body. The activation and degranulation of mast cells significantly modulates many aspects of physiological and pathological conditions in various settings. With respect to normal physiological functions, mast cells ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2015.00620
更新日期:2016-01-06 00:00:00
abstract::The lymphatic vasculature plays a crucial role in regulating the inflammatory response by influencing drainage of extravasated fluid, inflammatory mediators, and leukocytes. Lymphatic vessels undergo pronounced enlargement in inflamed tissue and display increased leakiness, indicating reduced functionality. Interferin...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.00308
更新日期:2019-02-26 00:00:00
abstract::Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage. MDSCs expand in pathological situations, such as chronic infection, cancer, autoimmunity, and allograft rejection. As chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantatio...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.00900
更新日期:2019-04-26 00:00:00
abstract::Objectives: Regulatory T cells (Tregs) are frequently functionally impaired in patients with granulomatosis with polyangiitis (GPA). However, the mechanism underlying their impaired function is unknown. Here, we hypothesized that Treg dysfunction in GPA is due to altered microRNA (miRNA) expression. Methods: RNA isola...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02170
更新日期:2019-09-12 00:00:00