• Fisheries and Aquatic Sciences
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• v.20 no.12
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• pp.31.1-31.11
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• 2017

Background: Liver-expressed antimicrobial peptide-2 (LEAP-2) is an important component of innate immune system in teleosts. In order to understand isoform-specific involvement and regulation of LEAP-2 genes in mud loach (Misgurnus mizolepis, Cypriniformes), a commercially important food fish, this study was aimed to characterize gene structure and expression characteristics of two paralog LEAP-2 isoforms. Results: Mud loach LEAP-2 isoforms (LEAP-2A and LEAP-2B) showed conserved features in the core structure of mature peptides characterized by four Cys residues to form two disulfide bonds. The two paralog isoforms represented a tripartite genomic organization, known as a common structure of vertebrate LEAP-2 genes. Bioinformatic analysis predicted various transcription factor binding motifs in the 5'-flanking regions of mud loach LEAP-2 genes with regard to development and immune response. Mud loach LEAP-2A and LEAP-2B isoforms exhibited different tissue expression patterns and were developmentally regulated. Both isoforms are rapidly modulated toward upregulation during bacterial challenge in an isoform and/or tissue-dependent fashion. Conclusion: Both LEAP-2 isoforms play protective roles not only in embryonic and larval development but also in early immune response to bacterial invasion in mud loach. The regulation pattern of the two isoform genes under basal and stimulated conditions would be isoform-specific, suggestive of a certain degree of functional divergence between isoforms in innate immune system in this species.

• IMMUNE NETWORK
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• v.21 no.3
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• pp.18.1-18.13
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• 2021

TLR signaling is critical for broad scale immune recognition of pathogens and/or danger molecules. TLRs are particularly important for the activation and the maturation of cells comprising the innate immune response. In recent years it has become apparent that several different TLRs regulate the function of lymphocytes as well, albeit to a lesser degree compared to innate immunity. TLR2 heterodimerizes with either TLR1 or TLR6 to broadly recognize bacterial lipopeptides as well as several danger-associated molecular patterns. In general, TLR2 signaling promotes immune cell activation leading to tissue inflammation, which is advantageous for combating an infection. Conversely, inappropriate or dysfunctional TLR2 signaling leading to an overactive inflammatory response could be detrimental during sterile inflammation and autoimmune disease. This review will highlight and discuss recent research advances linking TLR2 engagement to autoimmune inflammation.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.11.1-11.26
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• 2022

When epithelial cells are exposed to potentially threatening external stimuli such as allergens, bacteria, viruses, and helminths, they instantly produce "alarmin" cytokines, namely, IL-33, IL-25, and TSLP. These alarmins alert the immune system about these threats, thereby mobilizing host immune defense mechanisms. Specifically, the alarmins strongly stimulate type-2 immune cells, including eosinophils, mast cells, dendritic cells, type-2 helper T cells, and type-2 innate lymphoid cells. Given that the alarm-raising role of IL-33, IL-25, and TSLP was first detected in allergic and infectious diseases, most studies on alarmins focus on their role in these diseases. However, recent studies suggest that alarmins also have a broad range of effector functions in other pathological conditions, including psoriasis, multiple sclerosis, and cancer. Therefore, this review provides an update on the epithelium-derived cytokines in both allergic and non-allergic diseases. We also review the progress of clinical trials on biological agents that target the alarmins and discuss the therapeutic potential of these agents in non-allergic diseases.

• IMMUNE NETWORK
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• v.16 no.4
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• pp.249-255
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• 2016

Exogenous nucleic acids induce an innate immune response in mammalian host cells through activation of the retinoic acid-inducible gene I (RIG-I). We evaluated RIG-I protein for RNA binding and ATPase stimulation with RNA ligands to investigate the correlation with the extent of immune response through RIG-I activation in cells. RIG-I protein favored blunt-ended, double-stranded RNA (dsRNA) ligands over sticky-ended dsRNA. Moreover, the presence of the 5'-triphosphate (5'-ppp) moiety in dsRNA further enhanced binding affinity to RIG-I. Two structural motifs in RNA, blunt ends in dsRNA and 5'-ppp, stimulated the ATP hydrolysis activity of RIG-I. These structural motifs also strongly induced IFN expression as an innate immune response in cells. Therefore, we suggest that IFN induction through RIG-I activation is mainly determined by structural motifs in dsRNA that increase its affinity for RIG-I protein and stimulate ATPase activity in RIG-I.

• IMMUNE NETWORK
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• v.16 no.4
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• pp.211-218
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• 2016

Due to the increasing prevalence and number of life-threatening cases, food allergy has emerged as a major health concern. The classic immune response seen during food allergy is allergen-specific IgE sensitization and hypersensitivity reactions to foods occur in the effector phase with often severe and deleterious outcomes. Recent research has advanced understanding of the immunological mechanisms occurring during the effector phase of allergic reactions to ingested food. Therefore, this review will not only cover the mucosal immune system of the gastrointestinal tract and the immunological mechanisms underlying IgE-mediated food allergy, but will also introduce cells recently identified to have a role in the hypersensitivity reaction to food allergens. These include IL-9 producing mucosal mast cells (MMC9s) and type 2 innate lymphoid cells (ILC2s). The involvement of these cell types in potentiating the type 2 immune response and developing the anaphylactic response to food allergens will be discussed. In addition, it has become apparent that there is a collaboration between these cells that contributes to an individual's susceptibility to IgE-mediated food allergy.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.9
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• pp.1516-1524
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• 2018

Objective: Defensins are a large family of antimicrobial peptides and components of the innate immune system that invoke an immediate immune response against harmful pathogens. Defensins are classified into alpha-, beta-, and theta-defensins. Avian species only possess beta-defensins (AvBDs), and approximately 14 AvBDs (AvBD1-AvBD14) have been identified in chickens to date. Although substantial information is available on the conservation and phylogenetics, limited information is available on the expression and regulation of AvBD8 in chicken immune tissues and cells. Methods: We examined AvBD8 protein expression in immune tissues of White Leghorn chickens (WL) by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-qPCR). In addition, we examined AvBD8 expression in chicken T-, B-, macrophage-, and fibroblast-cell lines and its regulation in these cells after lipopolysaccharide (LPS) treatment by immunocytochemistry and RT-qPCR. Results: Our results showed that chicken AvBD8 protein was strongly expressed in the WL intestine and in macrophages. AvBD8 gene expression was highly upregulated in macrophages treated with different LPS concentrations compared with that in T- and B-cell lines in a time-independent manner. Moreover, chicken AvBD8 strongly interacted with other AvBDs and with other antimicrobial peptides as determined by bioinformatics. Conclusion: Our study provides the expression and regulation of chicken AvBD8 protein in immune tissues and cells, which play crucial role in the innate immunity.

• Molecules and Cells
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• v.44 no.5
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• pp.301-309
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• 2021

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. ILCs can be categorized into three groups on the basis of the transcription factors that direct their functions and the cytokines they produce. Notably, these functions parallel the effector functions of T lymphocytes. ILCs play a frontline role in host defense and tissue homeostasis by responding rapidly to environmental factors, conducting effector responses in a tissue-specific manner, and interacting with hematopoietic and non-hematopoietic cells throughout the body. Moreover, recent studies reveal that ILCs are involved in development of various inflammatory diseases, such as respiratory diseases, autoimmune diseases, or cancer. In this review, we discuss the recent findings regarding the biology of ILCs in health and inflammatory diseases.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.293-299
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• 2013

20S-dihydroprotopanaxadiol (2H-PPD) is a derivative of protopanaxadiol, a glycone of ginsenosides prepared from Panax ginseng. Although ginsenosides and acidic polysaccharides are known to be major active ingredients in ginseng, the immunopharmacological activities of their metabolites and derivatives have not been fully explored. In this study, we aimed to elucidate the regulatory action of 2H-PPD on the function of monocytes and macrophages in innate immune responses. 2H-PPD was able to boost the phagocytic uptake of fluorescein isothiocyanate-dextran in macrophages and enhance the generation of radicals (reactive oxygen species) in sodium nitroprusside-treated RAW264.7 cells. The surface levels of the costimulatory molecules such as CD80 and CD86 were also increased during 2H-PPD treatment. In addition, this compound boosted U937 cell-cell aggregation induced by CD29 and CD43 antibodies, but not by cell-extracellular matrix (fibronectin) adhesion. Similarly, the surface levels of CD29 and CD43 were increased by 2H-PPD exposure. Therefore, our results strongly suggest that 2H-PPD has the pharmacological capability to upregulate the functional role of macrophages/monocytes in innate immunity.

• IMMUNE NETWORK
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• v.23 no.1
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• pp.8.1-8.13
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• 2023

CD8⁺ T cells are activated by TCRs that recognize specific cognate Ags, while NK-cell activation is regulated by a balance between signals from germline-encoded activating and inhibitory NK receptors. Through these different processes of Ag recognition, CD8⁺ T cells and NK cells play distinct roles as adaptive and innate immune cells, respectively. However, some human CD8⁺ T cells have been found to express activating or inhibitory NK receptors. CD8⁺ T-cell populations expressing NK receptors straddle the innate-adaptive boundary with their innate-like features. Recent breakthrough technical advances in multi-omics analysis have enabled elucidation of the unique immunologic characteristics of these populations. However, studies have not yet fully clarified the heterogeneity and immunological characteristics of each CD8⁺ T-cell population expressing NK receptors. Here we aimed to review the current knowledge of various CD8⁺ T-cell populations expressing NK receptors, and to pave the way for delineating the landscape and identifying the various roles of these T-cell populations.

• The Journal of Pediatrics of Korean Medicine
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• v.8 no.1
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• pp.39-58
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• 1994

Even though appropriate immune response is necessary for the survival of the individual, excessive or insufficient immune response might cause autoimmune or allergic disease respectively. So the immune response must be controlled to the degree that is beneficial for the well being of the individual. This study was undertaken to know the effects of Junsibaekchulsan(JB) on the immune system od the mouse. For the evalulation of the cell-mediated immunity(CMI), delayed-type hypersensitivity against dinitrofluorobenzene(DNFB) were measured, and humoral immunity, hemagglutinin and hemolysin titers against SRBCs(sheep red blood cells) were measured, and rosette formation of spleen cells with SRBCs were measured. For the evaluation of innate immunity, phagocytic activity of macrophages, natural killer cell activity, and reactive nitrogen and oxygen intermediates were measured. The results are as follows: 1. The administration of JB depressed the antibody formation (hemagglutinin and hemolysin) against SRBCs. 2. The administration of JB did not affect the delayed-type hypersensitivity against DNFB. 3. The administration of JB did not affect the cytotoxic activity of natural killer cells. 4. The administration of JB increased the phagocytic activity of macrophages. 5. The administration of JB increased the rosette formating cells of the spleen cells. 6. The exposure of JB induced the secretion of reactive nitrogen intermediates but administration of JB deperssed the production of reactive oxygen intermediates. Administration of JB selectively depressed the humoral immune response without affecting CMI and innate immunity. These results of JB on the immune system might be useful for the treatment of such.