Immunomodulatory Factors in Host Defense

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (15 February 2022) | Viewed by 36081

Special Issue Editor

Laboratory of Immunology and Infection Control, Institute of Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
Interests: antibody; mucosal defense; somatic hypermutation; gut microbiota

Special Issue Information

Dear Colleagues,

Our body itself is well organized to maintain homeostasis by sophisticated regulatory systems including nervous, metabolic, and circulatory systems. However, once exogenous materials are recognized by the host immune system, the expression and activation of proinflammatory cytokines, chemokines, and adhesion molecules will affect these systemic regulatory systems and sometimes disturb the homeostatic balance, resulting in diseases. Thus, further research is necessary to explore a new regulatory strategy of such inflammatory responses.

This Special Issue will welcome contributions focused on the interaction between host and exogenous materials including microorganisms and chemicals to unravel the bases of human disease.

Prof. Reiko Shinkura
Guest Editor

Manuscript Submission Information

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Keywords

  • cytokines
  • inflammation
  • antibody
  • lymphocytes
  • inflammatory cells
  • pathogen
  • microbiota
  • inflammatory diseases

Published Papers (11 papers)

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Research

Jump to: Review

14 pages, 2468 KiB  
Article
Role of Th17 Cytokines in the Liver’s Immune Response during Fatal Yellow Fever: Triggering Cell Damage Mechanisms
by Marcos Luiz Gaia Carvalho, Luiz Fábio Magno Falcão, Jeferson da Costa Lopes, Caio Cesar Henriques Mendes, Fábio Alves Olímpio, Vanessa do Socorro Cabral Miranda, Lais Carneiro dos Santos, Daniel Dias Pinheiro de Moraes, Marcos Virgilio Bertonsin Filho, Luccas Delgado da Costa, Raimunda do Socorro da Silva Azevedo, Ana Cecília Ribeiro Cruz, Vanessa Costa Alves Galúcio, Lívia Caricio Martins, Maria Irma Seixas Duarte, Arnaldo Jorge Martins Filho, Jorge Rodrigues de Sousa, Pedro Fernando da Costa Vasconcelos and Juarez Antônio Simões Quaresma
Cells 2022, 11(13), 2053; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11132053 - 28 Jun 2022
Viewed by 1549
Abstract
Yellow fever (YF) is an infectious and acute viral haemorrhagic disease that triggers a cascade of host immune responses. We investigated the Th17 cytokine profile in the liver tissue of patients with fatal YF. Liver tissue samples were collected from 26 deceased patients, [...] Read more.
Yellow fever (YF) is an infectious and acute viral haemorrhagic disease that triggers a cascade of host immune responses. We investigated the Th17 cytokine profile in the liver tissue of patients with fatal YF. Liver tissue samples were collected from 26 deceased patients, including 21 YF-positive and 5 flavivirus-negative patients, with preserved hepatic parenchyma architecture, who died of other causes. Histopathological and immunohistochemical analysis were performed on the liver samples to evaluate the Th17 profiles (ROR-γ, STAT3, IL-6, TGF-β, IL-17A, and IL-23). Substantial differences were found in the expression levels of these markers between the patients with fatal YF and controls. A predominant expression of Th17 cytokine markers was observed in the midzonal region of the YF cases, the most affected area in the liver acinus, compared with the controls. Histopathological changes in the hepatic parenchyma revealed cellular damage characterised mainly by the presence of inflammatory cell infiltrates, Councilman bodies (apoptotic cells), micro/macrovesicular steatosis, and lytic and coagulative necrosis. Hence, Th17 cytokines play a pivotal role in the immunopathogenesis of YF and contribute markedly to triggering cell damage in patients with fatal disease outcomes. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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15 pages, 3420 KiB  
Article
IFN-γ Induces PD-L1 Expression in Primed Human Basophils
by Srinivasa Reddy Bonam, Camille Chauvin, Mano J. Mathew and Jagadeesh Bayry
Cells 2022, 11(5), 801; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11050801 - 25 Feb 2022
Cited by 12 | Viewed by 3164
Abstract
Programmed death-ligand 1 (PD-L1) plays a key role in maintaining immune tolerance and also in immune evasion of cancers and pathogens. Though the identity of stimuli that induce PD-L1 in various human innate cells and their function are relatively well studied, data on [...] Read more.
Programmed death-ligand 1 (PD-L1) plays a key role in maintaining immune tolerance and also in immune evasion of cancers and pathogens. Though the identity of stimuli that induce PD-L1 in various human innate cells and their function are relatively well studied, data on the basophils remain scarce. In this study, we have identified one of the factors, such as IFN-γ, that induces PD-L1 expression in human basophils. Interestingly, we found that basophil priming by IL-3 is indispensable for IFN-γ-induced PD-L1 expression in human basophils. However, priming by other cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF) and thymic stromal lymphopoietin (TSLP) was dispensable. Analyses of a published microarray data set on IL-3-treated basophils indicated that IL-3 enhances IFNGR2, one of the chains of the IFNGR heterodimer complex, and CD274, thus providing a mechanistic insight into the role of IL-3 priming in IFN-γ-induced PD-L1 expression in human basophils. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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12 pages, 1523 KiB  
Article
HIF-1α Stabilization in Flagellin-Stimulated Human Bronchial Cells Impairs Barrier Function
by Ivan Ramirez-Moral, Bianca L. Ferreira, Joe M. Butler, Michel van Weeghel, Natasja A. Otto, Alex F. de Vos, Xiao Yu, Menno D. de Jong, Riekelt H. Houtkooper and Tom van der Poll
Cells 2022, 11(3), 391; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11030391 - 24 Jan 2022
Cited by 1 | Viewed by 2572
Abstract
The respiratory epithelium provides a first line of defense against pathogens. Hypoxia-inducible factor (HIF)1α is a transcription factor which is stabilized in hypoxic conditions through the inhibition of prolyl-hydroxylase (PHD)2, the enzyme that marks HIF1α for degradation. Here, we studied the impact of [...] Read more.
The respiratory epithelium provides a first line of defense against pathogens. Hypoxia-inducible factor (HIF)1α is a transcription factor which is stabilized in hypoxic conditions through the inhibition of prolyl-hydroxylase (PHD)2, the enzyme that marks HIF1α for degradation. Here, we studied the impact of HIF1α stabilization on the response of primary human bronchial epithelial (HBE) cells to the bacterial component, flagellin. The treatment of flagellin-stimulated HBE cells with the PHD2 inhibitor IOX2 resulted in strongly increased HIF1α expression. IOX2 enhanced the flagellin-induced expression of the genes encoding the enzymes involved in glycolysis, which was associated with the intracellular accumulation of pyruvate. An untargeted pathway analysis of RNA sequencing data demonstrated the strong inhibitory effects of IOX2 toward key innate immune pathways related to cytokine and mitogen-activated kinase signaling cascades in flagellin-stimulated HBE cells. Likewise, the cell–cell junction organization pathway was amongst the top pathways downregulated by IOX2 in flagellin-stimulated HBE cells, which included the genes encoding claudins and cadherins. This IOX2 effect was corroborated by an impaired barrier function, as measured by dextran permeability. These results provide a first insight into the effects associated with HIF1α stabilization in the respiratory epithelium, suggesting that HIF1α impacts properties that are key to maintaining homeostasis upon stimulation with a relevant bacterial agonist. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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17 pages, 2568 KiB  
Article
Adjunctive Thymosin Beta-4 Treatment Influences PMN Effector Cell Function during Pseudomonas aeruginosa-Induced Corneal Infection
by Yuxin Wang, Thomas W. Carion, Abdul Shukkur Ebrahim, Gabriel Sosne and Elizabeth A. Berger
Cells 2021, 10(12), 3579; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10123579 - 18 Dec 2021
Cited by 6 | Viewed by 2628
Abstract
Previous work examining the therapeutic efficacy of adjunct thymosin beta 4 (Tβ4) to ciprofloxacin for ocular infectious disease has revealed markedly reduced inflammation (inflammatory mediators and innate immune cells) with increased activation of wound healing pathways. Understanding the therapeutic mechanisms of action have [...] Read more.
Previous work examining the therapeutic efficacy of adjunct thymosin beta 4 (Tβ4) to ciprofloxacin for ocular infectious disease has revealed markedly reduced inflammation (inflammatory mediators and innate immune cells) with increased activation of wound healing pathways. Understanding the therapeutic mechanisms of action have further revealed a synergistic effect with ciprofloxacin to enhance bacterial killing along with a regulatory influence over macrophage effector cell function. As a natural extension of the aforementioned work, the current study uses an experimental model of P. aeruginosa-induced keratitis to examine the influence of Tβ4 regarding polymorphonuclear leukocyte (PMN/neutrophil) cellular function, contributing to improved disease response. Flow cytometry was utilized to phenotypically profile infiltrating PMNs after infection. The generation of reactive oxygen species (ROS), neutrophil extracellular traps (NETs), and PMN apoptosis were investigated to assess the functional activities of PMNs in response to Tβ4 therapy. In vitro work using peritoneal-derived PMNs was similarly carried out to verify and extend our in vivo findings. The results indicate that the numbers of infiltrated PMNs into infected corneas were significantly reduced with adjunctive Tβ4 treatment. This was paired with the downregulated expression of proinflammatory markers on these cells, as well. Data generated from PMN functional studies suggested that the corneas of adjunctive Tβ4 treated B6 mice exhibit a well-regulated production of ROS, NETs, and limited PMN apoptosis. In addition to confirming the in vivo results, the in vitro findings also demonstrated that neutrophil elastase (NE) was unnecessary for NETosis. Collectively, these data provide additional evidence that adjunctive Tβ4 + ciprofloxacin treatment is a promising option for bacterial keratitis that addresses both the infectious pathogen and cellular-mediated immune response, as revealed by the current study. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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26 pages, 5943 KiB  
Article
Escherichia coli and Staphylococcus aureus Differentially Regulate Nrf2 Pathway in Bovine Mammary Epithelial Cells: Relation to Distinct Innate Immune Response
by Yi-Tian Ying, Jing Yang, Xun Tan, Rui Liu, Ying Zhuang, Jia-Xue Xu and Wei-Jia Ren
Cells 2021, 10(12), 3426; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10123426 - 06 Dec 2021
Cited by 9 | Viewed by 2885
Abstract
Escherichia coli and Staphylococcus aureus are major mastitis causing pathogens in dairy cattle but elicit distinct immune and an inflammatory response in the udder. However, the host determinants responsible for this difference remains largely unknown. Our initial studies focused on the global transcriptomic [...] Read more.
Escherichia coli and Staphylococcus aureus are major mastitis causing pathogens in dairy cattle but elicit distinct immune and an inflammatory response in the udder. However, the host determinants responsible for this difference remains largely unknown. Our initial studies focused on the global transcriptomic response of primary bovine mammary epithelial cells (pbMECs) to heat-killed E. coli and S. aureus. RNA-sequencing transcriptome analysis demonstrates a significant difference in expression profiles induced by E. coli compared with S. aureus. A major differential response was the activation of innate immune response by E. coli, but not by S. aureus. Interestingly, E. coli stimulation increased transcript abundance of several genes downstream of Nrf2 (nuclear factor erythroid 2-related factor 2) that were enriched in gene sets with a focus on metabolism and immune system. However, none of these genes was dysregulated by S. aureus. Western blot analysis confirms that S. aureus impairs Nrf2 activation as compared to E. coli. Using Nrf2-knockdown cells we demonstrate that Nrf2 is necessary for bpMECs to mount an effective innate defensive response. In support of this notion, nuclear Nrf2 overexpression augmented S. aureus-stimulated inflammatory response. We also show that, unlike E. coli, S. aureus disrupts the non-canonical p62/SQSTM1-Keap1 pathway responsible for Nrf2 activation through inhibiting p62/SQSTM1 phosphorylation at S349. Collectively, our findings provide important insights into the contribution of the Nrf2 pathway to the pathogen-species specific immune response in bovine mammary epithelial cells and raise a possibility that impairment of Nrf2 activation contributes to, at least in part, the weak inflammatory response in S. aureus mastitis. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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13 pages, 1168 KiB  
Article
Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38
by Jeonghyun Lee, Kyong-Oh Shin, Yesol Kim, Jaewon Cho, Hyung W. Lim, Sung-Il Yoon, Geun-Shik Lee, Hyun-Jeong Ko, Pyeung-Hyeun Kim, Yoshikazu Uchida, Kyungho Park and Seung Goo Kang
Cells 2020, 9(6), 1561; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9061561 - 26 Jun 2020
Cited by 4 | Viewed by 3585
Abstract
The effector function of tumor-infiltrated CD4+ T cells is readily suppressed by many types of immune regulators in the tumor microenvironment, which is one of the major mechanisms of immune tolerance against cancer. Cathelicidin-related antimicrobial peptide (CRAMP), the mouse analog of LL-37 [...] Read more.
The effector function of tumor-infiltrated CD4+ T cells is readily suppressed by many types of immune regulators in the tumor microenvironment, which is one of the major mechanisms of immune tolerance against cancer. Cathelicidin-related antimicrobial peptide (CRAMP), the mouse analog of LL-37 peptide in humans, is a cationic antimicrobial peptide belonging to the cathelicidin family; however, its secretion by cancer cells and role in the tumor microenvironment (TME) remain unclear. In this study, we explored the possibility of an interaction between effector CD4+ T cells and CRAMP using in vitro-generated mouse Th17 cells. We found that CRAMP stimulates Th17 cells to express the ectonucleotidase CD73, while simultaneously inducing cell death. This finding suggested that CD73-expressing Th17 cells may function as immune suppressor cells instead of effector cells. In addition, treatment of pharmacological inhibitors of the transforming growth factor-beta (TGF-β) signaling pathway showed that induction of CD73 expression is mediated by the p38 signaling pathway. Overall, our findings suggest that tumor-derived LL-37 likely functions as an immune suppressor that induces immune tolerance against tumors through shaping effector Th17 cells into suppressor Th17 cells, suggesting a new intervention target to improve cancer immunotherapy. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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16 pages, 2423 KiB  
Article
In Vitro Effects of Streptococcus oralis Biofilm on Peri-Implant Soft Tissue Cells
by Alexandra Ingendoh-Tsakmakidis, Jörg Eberhard, Christine S. Falk, Meike Stiesch and Andreas Winkel
Cells 2020, 9(5), 1226; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9051226 - 15 May 2020
Cited by 13 | Viewed by 3635
Abstract
Human gingival epithelial cells (HGEps) and fibroblasts (HGFs) are the main cell types in peri-implant soft tissue. HGEps are constantly exposed to bacteria, but HGFs are protected by connective tissue as long as the mucosa–implant seal is intact. Streptococcus oralis is one of [...] Read more.
Human gingival epithelial cells (HGEps) and fibroblasts (HGFs) are the main cell types in peri-implant soft tissue. HGEps are constantly exposed to bacteria, but HGFs are protected by connective tissue as long as the mucosa–implant seal is intact. Streptococcus oralis is one of the commensal bacteria, is highly abundant at healthy implant sites, and might modulate soft tissue cells—as has been described for other streptococci. We have therefore investigated the effects of the S. oralis biofilm on HGEps and HGFs. HGEps or HGFs were grown separately on titanium disks and responded to challenge with S. oralis biofilm. HGFs were severely damaged after 4 h, exhibiting transcriptional inflammatory and stress responses. In contrast, challenge with S. oralis only induced a mild transcriptional inflammatory response in HGEps, without cellular damage. HGFs were more susceptible to the S. oralis biofilm than HGEps. The pro-inflammatory interleukin 6 (IL-6) was attenuated in HGFs, as was interleukin 8 (CXCL8) in HGEps. This indicates that S. oralis can actively protect tissue. In conclusion, commensal biofilms can promote homeostatic tissue protection, but only if the implant–mucosa interface is intact and HGFs are not directly exposed. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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13 pages, 2838 KiB  
Article
Helicobacter pylori Induces IL-33 Production and Recruits ST-2 to Lipid Rafts to Exacerbate Inflammation
by Chia-Jung Kuo, Chun-Ya Chen, Horng-Ren Lo, Chun-Lung Feng, Hui-Yu Wu, Mei-Zi Huang, Tung-Nan Liao, Yu-An Chen and Chih-Ho Lai
Cells 2019, 8(10), 1290; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8101290 - 21 Oct 2019
Cited by 16 | Viewed by 4594
Abstract
Helicobacter pylori colonizes human gastric epithelial cells and contributes to the development of several gastrointestinal disorders. Interleukin (IL)-33 is involved in various immune responses, with reported proinflammatory and anti-inflammatory effects, which may be associated with colitis and colitis-associated cancer. IL-33 induces the inflammatory [...] Read more.
Helicobacter pylori colonizes human gastric epithelial cells and contributes to the development of several gastrointestinal disorders. Interleukin (IL)-33 is involved in various immune responses, with reported proinflammatory and anti-inflammatory effects, which may be associated with colitis and colitis-associated cancer. IL-33 induces the inflammatory cascade through its receptor, suppression of tumorigenicity-2 (ST-2). Binding of IL-33 to membrane-bound ST-2 (mST-2) recruits the IL-1 receptor accessory protein (IL-1RAcP) and activates intracellular signaling pathways. However, whether IL-33/ST-2 is triggered by H. pylori infection and whether this interaction occurs in lipid rafts remain unclear. Our study showed that both IL-33 and ST-2 expression levels were significantly elevated in H. pylori-infected cells. Confocal microscopy showed that ST-2 mobilized into the membrane lipid rafts during infection. Depletion of membrane cholesterol dampened H. pylori-induced IL-33 and IL-8 production. Furthermore, in vivo studies revealed IL-33/ST-2 upregulation, and severe leukocyte infiltration was observed in gastric tissues infected with H. pylori. Together, these results demonstrate that ST-2 recruitment into the lipid rafts serves as a platform for IL-33-dependent H. pylori infection, which aggravates inflammation in the stomach. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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22 pages, 15709 KiB  
Article
Paraimmunobiotic Bifidobacteria Modulate the Expression Patterns of Peptidoglycan Recognition Proteins in Porcine Intestinal Epitheliocytes and Antigen Presenting Cells
by Hikaru Iida, Masanori Tohno, Md. Aminul Islam, Nana Sato, Hisakazu Kobayashi, Leonardo Albarracin, AKM Humayun Kober, Wakako Ikeda-Ohtsubo, Yoshihito Suda, Hisashi Aso, Tomonori Nochi, Ayako Miyazaki, Hirohide Uenishi, Noriyuki Iwabuchi, Jin-zhong Xiao, Julio Villena and Haruki Kitazawa
Cells 2019, 8(8), 891; https://0-doi-org.brum.beds.ac.uk/10.3390/cells8080891 - 14 Aug 2019
Cited by 5 | Viewed by 5360
Abstract
Peptidoglycan recognition proteins (PGLYRPs) are a family of pattern recognition receptors (PRRs) that are able to induce innate immune responses through their binding to peptidoglycan (PGN), lipopolysaccharide, or lipoteichoic acid, or by interacting with other PRR-ligands. Recently, progress has been made in understanding [...] Read more.
Peptidoglycan recognition proteins (PGLYRPs) are a family of pattern recognition receptors (PRRs) that are able to induce innate immune responses through their binding to peptidoglycan (PGN), lipopolysaccharide, or lipoteichoic acid, or by interacting with other PRR-ligands. Recently, progress has been made in understanding the immunobiology of PGLYRPs in human and mice, however, their functions in livestock animals have been less explored. In this study, we characterized the expression patterns of PGLYRPs in porcine intestinal epithelial (PIE) cells and antigen-presenting cells (APCs) and their modulation by the interactions of host cells with PRR-ligands and non-viable immunomodulatory probiotics referred to as paraimmunobiotics. We demonstrated that PGLYRP-1, -2, -3, and -4 are expressed in PIE cells and APCs from Peyer’s patches, being PGLYPR-3 and -4 levels higher than PGLYRP-1 and -2. We also showed that PGLYRPs expression in APCs and PIE cells can be modulated by different PRR agonists. By using knockdown PIE cells for TLR2, TLR4, NOD1, and NOD2, or the four PGLYRPs, we demonstrated that PGLYRPs expressions would be required for activation and functioning of TLR2, TLR4, NOD1, and NOD2 in porcine epitheliocytes, but PGLYRPs activation would be independent of those PRR expressions. Importantly, we reported for the first time that PGLYRPs expression can be differentially modulated by paraimmunobiotic bifidobacteria in a strain-dependent manner. These results provide evidence for the use of paraimmunobiotic bifidobacteria as an alternative for the improvement of resistance to intestinal infections or as therapeutic tools for the reduction of the severity of inflammatory damage in diseases in which a role of PGLYRPs-microbe interaction has been demonstrated. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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Review

Jump to: Research

15 pages, 794 KiB  
Review
The Regulatory Activity of Noncoding RNAs in ILCs
by Alessio Grimaldi, Giuseppe Pietropaolo, Helena Stabile, Andrea Kosta, Cristina Capuano, Angela Gismondi, Angela Santoni, Giuseppe Sciumè and Cinzia Fionda
Cells 2021, 10(10), 2742; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10102742 - 14 Oct 2021
Cited by 5 | Viewed by 2036
Abstract
Innate lymphoid cells (ILCs) are innate lymphocytes playing essential functions in protection against microbial infections and participate in both homeostatic and pathological contexts, including tissue remodeling, cancer, and inflammatory disorders. A number of lineage-defining transcription factors concurs to establish transcriptional networks which determine [...] Read more.
Innate lymphoid cells (ILCs) are innate lymphocytes playing essential functions in protection against microbial infections and participate in both homeostatic and pathological contexts, including tissue remodeling, cancer, and inflammatory disorders. A number of lineage-defining transcription factors concurs to establish transcriptional networks which determine the identity and the activity of the distinct ILC subsets. However, the contribution of other regulatory molecules in controlling ILC development and function is also recently emerging. In this regard, noncoding RNAs (ncRNAs) represent key elements of the complex regulatory network of ILC biology and host protection. ncRNAs mostly lack protein-coding potential, but they are endowed with a relevant regulatory activity in immune and nonimmune cells because of their ability to control chromatin structure, RNA stability, and/or protein synthesis. Herein, we summarize recent studies describing how distinct types of ncRNAs, mainly microRNAs, long ncRNAs, and circular RNAs, act in the context of ILC biology. In particular, we comment on how ncRNAs can exert key effects in ILCs by controlling gene expression in a cell- or state-specific manner and how this tunes distinct functional outputs in ILCs. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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14 pages, 1879 KiB  
Review
Xenopus Interferon Complex: Inscribing the Amphibiotic Adaption and Species-Specific Pathogenic Pressure in Vertebrate Evolution?
by Yun Tian, Jordan Jennings, Yuanying Gong and Yongming Sang
Cells 2020, 9(1), 67; https://0-doi-org.brum.beds.ac.uk/10.3390/cells9010067 - 26 Dec 2019
Cited by 7 | Viewed by 3129
Abstract
Several recent studies have revealed previously unknown complexity of the amphibian interferon (IFN) system. Being unique in vertebrate animals, amphibians not only conserve and multiply the fish-like intron-containing IFN genes, but also rapidly evolve amniote-like intronless IFN genes in each tested species. We [...] Read more.
Several recent studies have revealed previously unknown complexity of the amphibian interferon (IFN) system. Being unique in vertebrate animals, amphibians not only conserve and multiply the fish-like intron-containing IFN genes, but also rapidly evolve amniote-like intronless IFN genes in each tested species. We postulate that the amphibian IFN system confers an essential model to study vertebrate immune evolution in molecular and functional diversity to cope with unprecedented pathophysiological requirement during terrestrial adaption. Studies so far have ascribed a potential role of these IFNs in immune regulation against intracellular pathogens, particularly viruses; however, many knowledge gaps remain elusive. Based on recent reports about IFN’s multifunctional properties in regulation of animal physiological and defense responses, we interpret that amphibian IFNs may evolve novel function pertinent to their superior molecular diversity. Such new function revealed by the emerging studies about antifungal and developmental regulation of amphibian IFNs will certainly promote our understanding of immune evolution in vertebrates to address current pathogenic threats causing amphibian decline. Full article
(This article belongs to the Special Issue Immunomodulatory Factors in Host Defense)
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