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
David Shahnazaryan, Rana Khalil, Claire Wynne, Caroline A Jefferies, Joan Ní Gabhann-Dromgoole, Conor C Murphy
Herpes simplex keratitis (HSK), caused by herpes simplex virus type 1 (HSV-1) infection, is the commonest cause of infectious blindness in the developed world. Following infection the virus is initially suspended in the tear film, where it encounters a multi-pronged immune response comprising enzymes, complement, immunoglobulins and crucially, a range of anti-viral and pro-inflammatory cytokines. However, given that HSV-1 can overcome innate immune responses to establish lifelong latency throughout a susceptible individual's lifetime, there is significant interest in understanding the mechanisms employed by HSV-1 to downregulate the anti-viral type I interferon (IFN) mediated immune responses...
December 17, 2020: Scientific Reports
Meng-Shi Yang, Xiao-Jian Xu, Bin Zhang, Fei Niu, Bai-Yun Liu
The heterogeneity of traumatic brain injury (TBI)-induced secondary injury has greatly hampered the development of effective treatments for TBI patients. Targeting common processes across species may be an innovative strategy to combat debilitating TBI. In the present study, a cross-species transcriptome comparison was performed for the first time to determine the fundamental processes of secondary brain injury in Sprague-Dawley rat and C57/BL6 mouse models of TBI, caused by acute controlled cortical impact...
July 2021: Neural Regeneration Research
Ying Wu, Yongcan Zhou, Zhenjie Cao, Xiaojuan Chen, HeHe Du, Yun Sun
Vibrio harveyi is regarded as serious pathogen for marine fishes. However, host defense mechanisms involved in V. harveyi infection remain incompletely defined. The transcription factor IFN regulatory factor 7 (IRF7) is largely associated with host defense against viral infections, and the role of IRF7 during V. harveyi infection in fish has not been well illuminated previously. In this study, IRF7 from golden pompano (Trachinotus ovatus) was characterized (TroIRF7). The TroIRF7 gene is 1323 bp, which encodes 440 amino acid residues...
December 11, 2020: Developmental and Comparative Immunology
Biswas Neupane, Dhiraj Acharya, Farzana Nazneen, Gabriel Gonzalez-Fernandez, Alex Sutton Flynt, Fengwei Bai
Interferons (IFNs) are the key components of innate immunity and are crucial for host defense against viral infections. Here, we report a novel role of interleukin-17A (IL-17A) in inhibiting IFN-α2 expression thus promoting chikungunya virus (CHIKV) infection. CHIKV infected IL-17A deficient ( Il17a-/- ) mice expressed a higher level of IFN-α2 and developed diminished viremia and milder footpad swelling in comparison to wild-type (WT) control mice, which was also recapitulated in IL-17A receptor-deficient ( Il17ra-/- ) mice...
2020: Frontiers in Immunology
Ewa Leszczyńska, Edyta Makuch, Małgorzata Mitkiewicz, Izabella Jasyk, Miwako Narita, Sabina Górska, Tomasz Lipiński, Jakub Siednienko
Activation of TLR7 by small imidazoquinoline molecules such as R848 or R837 initiates signaling cascades leading to the activation of transcription factors, such as AP-1, NF-κB, and interferon regulatory factors (IRFs) and afterward to the induction of cytokines and anti-viral Type I IFNs. In general, TLRs mediate these effects by utilizing different intracellular signaling molecules, one of them is Mal. Mal is a protein closely related to the antibacterial response, and its role in the TLR7 pathways remains poorly understood...
November 25, 2020: International Journal of Molecular Sciences
Ying-Ying Chen, Yu-Feng Liu, Yong-Dong Liu, Xiao-Hui Deng, Jie Zhou
Hematopoietic stem cells (HSCs) maintain quiescence under steady state, however, they are compelled to proliferate and expand to replenish the blood system under stress. The molecular basis underlying stress hematopoiesis remains to be fully understood. In this study, we reported that IRF7 represents an important regulator of stress hematopoiesis. Interferon regulatory factor 7 (IRF7) was dispensable for normal hematopoiesis, whereas its deficiency significantly enhanced hematopoietic stem and progenitor cells (HSPCs) regeneration and improved long-term repopulation of HSCs under stress...
November 30, 2020: Stem Cells
Tao Li, Yiping Song, Xiuyu Bao, Jianqin Zhang
An increasing amount of evidence has revealed that microRNAs (miRNAs) participated in immune regulation and reaction to acute cold and heat stresses. As a new type of post-transcriptional regulatory factor, miRNA has received widespread attention; However, the specific mechanism used for this regulation still needs to be determined. In this study, thirty broilers at the same growth period were divided into three groups and treated with different temperature and humidity of CS (10-15 °C and 90% Relative Humidity (RH)), HS (39 °C and 90% RH), and NS (26 °C and 50-60% RH) respectively...
November 20, 2020: Animals: An Open Access Journal From MDPI
Yaoyao Zhu, Shijuan Shan, Huaping Zhao, Rongrong Liu, Hui Wang, Xinping Chen, Guiwen Yang, Hua Li
BACKGROUND: Interferon (IFN) regulatory factors (IRFs), as transcriptional regulatory factors, play important roles in regulating the expression of type I IFN and IFN- stimulated genes (ISGs) in innate immune responses. In addition, they participate in cell growth and development and regulate oncogenesis. RESULTS: In the present study, the cDNA sequence of IRF10 in common carp (Cyprinus carpio L.) was characterized (abbreviation, CcIRF10). The predicted protein sequence of CcIRF10 shared 52...
November 19, 2020: BMC Veterinary Research
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