Ian de Bus, Sandra van Krimpen, Guido J Hooiveld, Mark V Boekschoten, Mieke Poland, Renger Witkamp, Bauke Albada, Michiel Balvers
Docosahexaenoyl ethanolamide (DHEA), the ethanolamine conjugate of the n-3 long chain polyunsaturated fatty acid docosahexaenoic acid, is endogenously present in the human circulation and in tissues. Its immunomodulating properties have been (partly) attributed to an interaction with the cyclooxygenase-2 (COX-2) enzyme. Recently, we discovered that COX-2 converts DHEA into two oxygenated metabolites, 13- and 16-hydroxylated-DHEA (13- and 16-HDHEA, respectively). It remained unclear whether these oxygenated metabolites also display immunomodulating properties like their parent DHEA...
February 18, 2021: Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids
Guan-Feng Lu, Sheng-Cai Chen, Yuan-Peng Xia, Zi-Ming Ye, Fei Cao, Bo Hu
Inappropriate activation or overactivation of cyclic GMP-AMP synthase (cGAS) by double-stranded deoxyribonucleic acid (dsDNA) initiates a regulatory signaling cascade triggering a variety of inflammatory responses, which are a great threat to human health. This study focused on identifying the role of cGAS in atherosclerosis and its potential mechanisms. The relationship between cGAS and atherosclerosis was identified in an ApoE -/- mouse model. Meanwhile, RNA sequencing (RNA-seq) analysis of the underlying mechanisms of atherosclerosis in RAW264...
February 11, 2021: Aging
Yanyan Jiang, Yilin Liu, Yawen Zhao, Yiming Zheng, Meng Yu, Jianwen Deng, Hongjun Hao, Wei Zhang, Zhaoxia Wang, Yun Yuan
OBJECTIVE: This study aimed to investigate mitochondrial changes and the mitochondrial antiviral-signaling protein (MAVS)-type I interferon (IFN1) signaling pathway in the muscles of anti-melanoma differentiation gene 5(MDA5) dermatomyositis (DM) patients. METHODS: Eleven anti-MDA5 DM and ten antibody-negative DM patients were included. Muscle biopsies were performed in all patients. Muscle pathology and mitochondrial morphology in particular were compared between two groups...
February 12, 2021: Annals of Clinical and Translational Neurology
Anlong Qi, Tong Wang, Yanfen Chai, Jianning Zhang
OBJECTIVE: To explore the mechanism of complement 5a (C5a) in the pathogenesis of sepsis. METHODS: SPF male C57BL/6J mice were selected and divided into sham operation group (Sham group), cecal ligation and puncture (CLP) group and CLP+anti-C5A monoclonal antibody intervention group (CLP+anti-C5a group) according to random number table with 20 mice in each group. A CLP model was reproduced to induce sepsis, and those in the Sham group only underwent laparotomy without ligation and perforation...
January 2021: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
P Pradhan, R Toy, N Jhita, A Atalis, B Pandey, A Beach, E L Blanchard, S G Moore, D A Gaul, P J Santangelo, D M Shayakhmetov, K Roy
Innate immune responses to pathogens are driven by co-presentation of multiple pathogen-associated molecular patterns (PAMPs). Combinations of PAMPs can trigger synergistic immune responses, but the underlying molecular mechanisms of synergy are poorly understood. Here, we used synthetic particulate carriers co-loaded with monophosphoryl lipid A (MPLA) and CpG as pathogen-like particles (PLPs) to dissect the signaling pathways responsible for dual adjuvant immune responses. PLP-based co-delivery of MPLA and CpG to GM-CSF-driven mouse bone marrow-derived antigen-presenting cells (BM-APCs) elicited synergistic interferon-β (IFN-β) and interleukin-12p70 (IL-12p70) responses, which were strongly influenced by the biophysical properties of PLPs...
January 2021: Science Advances
Nicholas Agresti, Jacob P Lalezari, Phillip P Amodeo, Kabir Mody, Steven F Mosher, Harish Seethamraju, Scott A Kelly, Nader Z Pourhassan, C David Sudduth, Christopher Bovinet, Ahmed E ElSharkawi, Bruce K Patterson, Reejis Stephen, Jonah B Sacha, Helen L Wu, Seth A Gross, Kush Dhody
Coronavirus disease 2019 (COVID-19) is associated with considerable morbidity and mortality. The number of confirmed cases of infection with SARS-CoV-2, the virus causing COVID-19 continues to escalate with over 70 million confirmed cases and over 1.6 million confirmed deaths. Severe-to-critical COVID-19 is associated with a dysregulated host immune response to the virus, which is thought to lead to pathogenic immune dysregulation and end-organ damage. Presently few effective treatment options are available to treat COVID-19...
2021: Journal of translational autoimmunity
Jian Shang, Yuan Zheng, Jiayin Mo, Wenbiao Wang, Zhen Luo, Yongkui Li, Xulin Chen, Qiwei Zhang, Kailang Wu, Weiyong Liu, Jianguo Wu
Toll-like receptors (TLRs) are essential for the protection of the host from pathogen infections by initiating the integration of contextual cues to regulate inflammation and immunity. However, without tightly controlled immune responses, the host will be subjected to detrimental outcomes. Therefore, it is important to balance the positive and negative regulations of TLRs to eliminate pathogen infection, yet avert harmful immunological consequences. This study revealed a distinct mechanism underlying the regulation of TLR network...
January 31, 2021: Virulence
Yan Wang, Fuling Yang, Huadong Yin, Qijian He, Yuxiang Lu, Qing Zhu, Xi Lan, Xiaoling Zhao, Diyan Li, Yiping Liu, Hengyong Xu
In order to breed new birds with strong disease resistance, it is necessary to first understand the mechanism of avian antiviral response. Interferon regulatory factor 7 (IRF7) is not only a member of type I interferons (IFNs) regulatory factor (IRFs) family, but also a major regulator of the IFN response in mammals. However, whether IRF7 is involved in the host innate immune response remains unclear in poultry, due to the absence of IRF3. Here, we first observed by HE stains that with the increase of the time of ALV-J challenge, the thymus was obviously loose and swollen, the arrangement of liver cell was disordered, and the bursa of fabricius formed vacuolated...
January 23, 2021: Developmental and Comparative Immunology
Fan-Xiang Gao, Wei-Jia Lu, Yan Shi, Li Zhou, Jian-Fang Gui, Zhe Zhao
Interferon regulatory factor 7 (IRF7) is a key mediator in regulating the type Ι IFN response. Although irf7 has been identified in more than twenty fish species, alternative splicing has not been found in teleost irf7. Alternative splicing is an important mechanism expanding the transcriptomic and proteomic diversity, and has been found in several IRF family members. Here, three alternative splicing variants of irf7 were identified and characterized in obscure puffer. The first splicing transcript (Toirf7v1) was predicted to encode 428 amino acids with a DNA-binding domain (DBD), an interaction-associated domain (IAD) and a serine-rich domain (SRD)...
January 19, 2021: Developmental and Comparative Immunology
Azaria García-Ruvalcaba, Lourdes Del C Rizo de la Torre, María T Magaña-Torres, Ernesto Prado-Montes-de-Oca, Andrea V Ruiz-Ramírez, Héctor Rangel-Villalobos, José A Aguilar-Velázquez, Andrea M García-Muro, Josefina Y Sánchez-López
BACKGROUND: Early-onset diffuse gastric cancer (EODGC) occurs at or before 50 years of age. Pathogenic mutations and germline deletions in the CDH1 gene (E-cadherin) are well-documented genetic factors associated with the causes of EODGC. OBJECTIVE: The objective of the study was to study CDH1 germline variants and their potential functional impact in patients with EODGC in a Mexican population. METHODS: We studied seven EODGC patients from a biomedical research center in western Mexico...
January 19, 2021: Revista de Investigación Clínica; Organo del Hospital de Enfermedades de la Nutrición
Sangeetha Srinivasan, Julia E Babensee
Engineering a regulatory phenotype in dendritic cells (DCs) is a potential approach to circumvent an immune response against self-antigens in autoimmunity or alloantigens in allograft rejection. Cell microenvironments influence the differentiation of DC precursors into either proinflammatory/immunostimulatory or tolerogenic/regulatory DCs. Biomaterial-based vehicles can be used to re-engineer cell microenvironments and re-educate the DC phenotype. This study presents the development and validation of a biomaterial-based multicomponent immunomodulatory (MI) scaffold for the purpose of promoting a tolerogenic/regulatory DC phenotype...
July 13, 2020: ACS Biomaterials Science & Engineering
Evgeny Kiner, Elijah Willie, Brinda Vijaykumar, Kaitavjeet Chowdhary, Hugo Schmutz, Jodie Chandler, Alexandra Schnell, Pratiksha I Thakore, Graham LeGros, Sara Mostafavi, Diane Mathis, Christophe Benoist
CD4+ effector lymphocytes (Teff ) are traditionally classified by the cytokines they produce. To determine the states that Teff cells actually adopt in frontline tissues in vivo, we applied single-cell transcriptome and chromatin analyses to colonic Teff cells in germ-free or conventional mice or in mice after challenge with a range of phenotypically biasing microbes. Unexpected subsets were marked by the expression of the interferon (IFN) signature or myeloid-specific transcripts, but transcriptome or chromatin structure could not resolve discrete clusters fitting classic helper T cell (TH ) subsets...
January 18, 2021: Nature Immunology
Ye Seon Lim, Do-Young Lee, Hye-Yoon Kim, Yejin Ok, Seonyeong Hwang, Yuseok Moon, Sik Yoon
Epidermal growth factor‑like domain 8 (EGFL8), a newly identified member of the EGFL family, and plays negative regulatory roles in mouse thymic epithelial cells (TECs) and thymocytes. However, the role of EGFL8 in these cells remains poorly understood. In the present study, in order to characterize the function of EGFL8, genome‑wide expression profiles in EGFL8‑overexpressing or ‑silenced mouse cortical TECs (cTECs) were analyzed. Microarray analysis revealed that 458 genes exhibited a >2‑fold change in expression levels in the EGFL8‑overexpressing vs...
March 2021: International Journal of Molecular Medicine
Muyue Yang, Jipeng Li, Ping Gu, Xianqun Fan
The tumor development and metastasis are closely related to the structure and function of the tumor microenvironment (TME). Recently, TME modulation strategies have attracted much attention in cancer immunotherapy. Despite the preliminary success of immunotherapeutic agents, their therapeutic effects have been restricted by the limited retention time of drugs in TME. Compared with traditional delivery systems, nanoparticles with unique physical properties and elaborate design can efficiently penetrate TME and specifically deliver to the major components in TME...
July 2021: Bioactive Materials
Carolina Scagnolari, Alessandra Pierangeli, Federica Frasca, Camilla Bitossi, Agnese Viscido, Giuseppe Oliveto, Mirko Scordio, Laura Mazzuti, Daniele Di Carlo, Massimo Gentile, Angelo Solimini, Giancarlo Ceccarelli, Francesco Pugliese, Claudio Maria Mastroianni, Gabriella d'Ettorre, Ombretta Turriziani, Guido Antonelli
The natural course of type I and III interferon (IFN) response in the respiratory tract of COVID-19 patients needs to be better defined. We showed that type I/III IFNs, IFN-regulatory factor 7 (IRF-7), and IFN stimulated genes (ISGs), are highly expressed in the oropharyngeal cells of SARS-CoV-2 positive patients compared to healthy controls. Notably, the subgroup of critically-ill patients that required invasive mechanical ventilation had a general decrease in expression of IFN/ISG genes. Heterogeneous patterns of IFN-I/III response in the respiratory tract of COVID-19 patients may be associated to COVID-19 severity...
January 5, 2021: Virus Research
Matteo Vecellio, Liye Chen, Carla J Cohen, Adrian Cortes, Yan Li, Sarah Bonham, Carlo Selmi, Matthew A Brown, Roman Fischer, Julian C Knight, B Paul Wordsworth
OBJECTIVES: To investigate the functional consequences of the single nucleotide polymorphism rs4648889 in a putative enhancer upstream of the RUNX3 promoter associated with ankylosing spondylitis (AS). METHODS: The effects of rs4648889 on allele-specific transcription factor (TF) binding were investigated by DNA pull-down and quantitative mass spectrometry (qMS) with validation by electrophoretic mobility gel shift assays (EMSA), Western blot (WB) analysis of the pulled-down eluates, and chromatin immuno-precipitation (ChIP)-qPCR...
December 26, 2020: Arthritis & Rheumatology
Yang Liu, Xiaojia Liu, Na Zhang, Mingxiao Yin, Jingwen Dong, Qingxuan Zeng, Genxiang Mao, Danqing Song, Lu Liu, Hongbin Deng
Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blocking therapy has become a major pillar of cancer immunotherapy. Compared with antibodies targeting, small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed. Here we identified berberine (BBR), a proven anti-inflammation drug, as a negative regulator of PD-L1 from a set of traditional Chinese medicine (TCM) chemical monomers. BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells...
December 2020: Acta Pharmaceutica Sinica. B
Karam Ahmed Allam, Mostafa Mamdoh Haredy
INTRODUCTION: Van der Woude syndrome (VWS), an autosomal dominant condition associated with clefts of the lip and/or palate and lower lip pits, is caused by mutations in interferon regulatory factor 6 gene. It is reported to be the most common syndromic cleft worldwide. This case series presents the phenotypic characteristics and treatment outcomes in a group of 9 patients diagnosed with VWS. METHODS: A retrospective review was performed on records of patients given a diagnosis of VWS presenting to the Department of Plastic Surgery of Sohag University between July 2009 and November 2019...
December 16, 2020: Annals of Plastic Surgery
Benjamin M Liu, Harry R Hill
Coronavirus disease 2019 (COVID-19) has spread rapidly and become a pandemic. Caused by a novel human coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe COVID-19 is characterized by cytokine storm syndromes due to innate immune activation. Primary immunodeficiency (PID) cases represent a special patient population whose impaired immune system might make them susceptible to severe infections, posing a higher risk to COVID-19, but this could also lead to suppressed inflammatory responses and cytokine storm...
December 2020: Journal of Interferon & Cytokine Research
Lina Guo, Yang Zhang, Jinping Wang, Yingying Qi, Zongwang Zhang
Background: Interferon regulatory factor 8 (IRF8) is involved in the pathogenesis of neuropathic pain. However, whether and how IRF8 can regulate the nicotine withdrawal (NTW)-induced hyperalgesia has not been clarified. Methods: C57BL/6 mice were randomized and injected subcutaneously with saline (Control) or nicotine (3 mg/kg) three times per day for 7 consecutive days, followed by injection with mecamylamine to induce NTW. Their paw withdrawal latencies (PWLs) were measured, and the relative levels of IRF8 expression in the spinal cord tissues were determined longitudinally by western blot...
2020: Translational Neuroscience
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