• IMMUNE NETWORK
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• v.14 no.2
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• pp.67-72
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• 2014

The herpes virus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF), and therefore it is also known as TNFRSF14 or CD270 (1,2). In recent years, we have focused on understanding HVEM function in the mucosa of the intestine, particularly on the role of HVEM in colitis pathogenesis, host defense and regulation of the microbiota (2-4). HVEM is an unusual TNF receptor because of its high expression levels in the gut epithelium, its capacity to bind ligands that are not members of the TNF super family, including immunoglobulin (Ig) superfamily members BTLA and CD160, and its bi-directional functionality, acting as a signaling receptor or as a ligand for the receptor BTLA. Clinically, Hvem recently was reported as an inflammatory bowel disease (IBD) risk gene as a result of genome wide association studies (5,6). This suggests HVEM could have a regulatory role influencing the regulation of epithelial barrier, host defense and the microbiota. Consistent with this, using mouse models, we have revealed how HVEM is involved in colitis pathogenesis, mucosal host defense and epithelial immunity (3,7). Although further studies are needed, our results provide the fundamental basis for understanding why Hvem is an IBD risk gene, and they confirm that HVEM is a mucosal gatekeeper with multiple regulatory functions in the mucosa.

• Proceedings of the Korean Society for Applied Microbiology Conference
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• 2003.06a
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• pp.55-62
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• 2003

The mucosal immune system provides a first line of defense against invasion of infectious agents via inhalation, ingestion and sexual contact. For the induction of protective immunity at these invasion sites, one must consider the use of the CMIS, which interconnects inductive tissues, including PP and NALT, and effector tissues of the intestinal, respiratory and genitourinary tracts. In order for the CMIS to induce maximal protective mucosal immunity, co-administration of mucosal adjuvant or use of mucosal antigen delivery vehicle has been shown to be essential. When vaccine antigen is administered via oral or nasal route, antigen-specific Th 1 and Th2 cells, cytotoxic T lymphocytes(CTLs) and IgA B cell responses are effectively induced by the CMIS. In the early stages of induction of mucosal immune response, the uptake of orally or nasally administered antigens is achieved through a unique set of antigen-sampling cells, M cells located in follicle-associated epithelium(FAE) of inductive sites. After successful uptake, the antigens are immediately processed and presented by the underlying DCs for the generation of antigen-specific T cells and IgA committed B cells. These antigen-specific lymphocytes are then home to the distant mucosal effector tissues for the induction of antigen-specific humoral(e.g., IgA) and cell-mediated (e.g., CTL and Th1) immune responses in order to form the first line of defense. Elucidation of the molecular/cellular characteristics of the immunological sequence of mucosal immune response beginning from the antigen sampling and processing/presentation by M cells and mucosal DCs followed by the effector phase with antigen-specific lymphocytes will greatly facilitate the design of a new generation of effective mucosal antigen-specific lymphocytes will greatly facilitate the design of a new generation of a new generation of effective mucosal adjuvants and of a vaccine deliver vehicle that maximizes the use of the CMIS.

• Nutritional Sciences
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• v.7 no.1
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• pp.31-34
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• 2004

This paper reviews the effects of Spirulina platensis and its extracts and phycocyanin, a blue photosynthetic pigment protein in Spirulina on the mucosal immune functions in humans and animals as follows: TEX>$\bullet$ IgA antibody response and other classes in mucosal immunity of mice treated with Spirulina platensis and its extract. $\bullet$ Effect of Spirulina phycocyanin ingestion on the mucosal antibody responses in mice. - Distinct effects of phycocyanin on secretory IgA and allergic IgE antibody responses in mice following oral immunization with antigen-entrapped biodegradable microparticles. $\bullet$ Influence of dietary Spirulina platensis on IgA level in human saliva. $\bullet$ A study on enhancement of bone-marrow cell-proliferation and differentiation by Spirulina platensis in mice: in vivo and in vitro study

• IMMUNE NETWORK
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• v.15 no.1
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• pp.44-49
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• 2015

Interactions between microbes and epithelial cells in the gastrointestinal tract are closely associated with regulation of intestinal mucosal immune responses. Recent studies have highlighted the modulation of mucosal immunity by microbe-derived molecules such as ATP and short-chain fatty acids. In this study, we undertook to characterize the expression of the ATP-gated $P2X_7$ receptor ($P2X_7R$) on M cells and its role in gastrointestinal mucosal immune regulation because it was poorly characterized in Peyer's patches, although purinergic signaling via $P2X_7R$ and luminal ATP have been considered to play an important role in the gastrointestinal tract. Here, we present the first report on the expression of $P2X_7R$ on M cells and characterize the role of $P2X_7R$ in immune enhancement by ATP or LL-37.

• IMMUNE NETWORK
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• v.13 no.4
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• pp.157-162
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• 2013

Application of vaccine materials through oral mucosal route confers great economical advantage in animal farming industry due to much less vaccination cost compared with that of injection-based vaccination. In particular, oral administration of recombinant protein antigen against foot-and- mouth disease virus (FMDV) is an ideal strategy because it is safe from FMDV transmission during vaccine production and can induce antigen-specific immune response in mucosal compartments, where FMDV infection has been initiated, which is hardly achievable through parenteral immunization. Given that effective delivery of vaccine materials into immune inductive sites is prerequisite for effective oral mucosal vaccination, M cell-targeting strategy is crucial in successful vaccination since M cells are main gateway for luminal antigen influx into mucosal lymphoid tissue. Here, we applied previously identified M cell-targeting ligand Co1 to VP1 of FMDV in order to test the possible oral mucosal vaccination against FMDV infection. M cell-targeting ligand Co1-conjugated VP1 interacted efficiently with M cells of Peyer's patch. In addition, oral administration of ligand-conjugated VP1 enhanced the induction of VP1-specific IgG and IgA responses in systemic and mucosal compartments, respectively, in comparison with those from oral administration of VP1 alone. In addition, the enhanced VP1-specific immune response was found to be due to antigen-specific Th2-type cytokine production. Collectively, it is suggested that the M cell-targeting strategy could be applied to develop efficient oral mucosal vaccine against FMDV infection.

• Proceedings of the Korea Society of Poultry Science Conference
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• 2006.11a
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• pp.7-16
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• 2006

Poultry products including meat and eggs constitute a major protein source in the American diet and disease - causing pathogens represent major challenges to the poultry industry. More than 95 % of pathogens enter the host through the mucosal surfaces of the respiratory, digestive and reproductive tracts and over the past few decades, the two main mechanisms used to control diseases have been the use of vaccines and antibiotics. However, in the poultry industry, there are mounting concerns over the ability of current vaccines to adequately protect against emerging hyper - virulent strains of pathogens and a lack of suitable, cost effective adjuvants. Thorough investigation of the immunogenetic responses involved in host-pathogen interactions will lead to the development of new and effective strategies for improving poultry health, food safety and the economic viability of the US poultry industry. In this paper, I describe the development of immunogenomic and proteomic tools to fundamentally determine and characterize the immunological mechanisms of the avian host to economically significant mucosal pathogens such as Eimeria. Recent completion of poultry genome sequencing and the development of several tissue-specific cDNA libraries in chickens are facilitating the rapid application of functional immunogenomics in the poultry disease research. Furthermore, research involving functional genomics, immunology and bioinformatics is providing novel insights into the processes of disease and immunity to microbial pathogens at mucosal surfaces. In this presentation, a new strategy of global gene expression using avian macrophage (AMM) to characterize the multiple pathways related to the variable immune responses of the host to Eimeria is described. This functional immunogenomics approach will increase current understanding of how mucosal immunity to infectious agents operates, and how it may be enhanced to enable the rational development of new and effective strategies against coccidiosis and other mucosal pathogens.

• Journal of Microbiology and Biotechnology
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• v.22 no.7
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• pp.907-916
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• 2012

Burkholderia cepacia is an important pathogen that often causes pneumonia in immunocompromised individuals. Here, it was demonstrated that the TLR5 agonist flagellin could locally activate innate immunity. This was characterized by rapid expressions of IL-$1{\beta}$, TNF-${\alpha}$, and iNOS mRNA and a delay in the expression of IL-10 mRNA. A significant elevation in the IL-$1{\beta}$, TNF-${\alpha}$, and nitric oxide levels was also noted. In the respiratory tract, flagellin induced neutrophil infiltration into the airways, which was observed by histopathological examination and confirmed by the neutrophil count and level of myeloperoxidase activity. This was concomitant with a high activity of alveolar macrophages that engulfed and killed B. cepacia in vitro. The flagellin mucosal treatment improved the B. cepacia clearance in the mouse lung. Thus, the present findings illustrate the profound stimulatory effect of flagellin on the lung mucosal innate immunity, a response that needs to be exploited therapeutically to prevent the development of respiratory tract infection by B. cepacia.

• Korean Journal of Poultry Science
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• v.38 no.4
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• pp.275-284
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• 2011

As the world population grows and developing countries become more affluent, the global consumption of meat will increase by more than 50% within the next 10 years. Confronting the increased demand for poultry food products are emerging field diseases, increasing regulatory bans of antimicrobial growth promoters, high-density growth conditions, and waste management. Although biotechnology offers solutions to some of these challenges, basic studies are needed to better understand the complex interaction between the intestinal microbiome, host immunity and the environment. This presentation will focus on emerging strategies to enhance gut immunity and to decrease economic losses due to poultry diseases. This presentation will highlight recent developments in coccidiosis research and provide information on host immunity, immunomodulation, and the latest advances in dietary and nutritional approaches against coccidiosis. Such information will magnify our understanding of host-parasite biology, mucosal immunology, and design of future nutritional interventions and vaccination strategies for coccidiosis.

• Journal of Life Science
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• v.32 no.1
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• pp.36-43
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• 2022

Mucosal immunity is a well-designed defense system that builds precise and dynamic relationships against pathogens, and the gastrointestinal tract is the most important organ with this system, acting as a guardian at the forefront of its activity. Salmonella spp. cause food poisoning, entering the body orally and mainly invading the Peyer's patches of the small intestine. Although Salmonella strains share similar mechanisms for inducing innate immunity, different serotypes may have different effects on the intestinal mucosa due to host specificities and pathogenicity. In this study, we evaluated the effects of Salmonella enteritidis infections in mouse intestine and observed significantly reduced dose-dependent survival rates in a challenge test. Flow cytometry data showed no significant differences in intestinal immune cell populations, although histology indicated increased mucin production and decreased goblet cell counts in the Salmonella-treated groups. Furthermore, Claudin expression was significantly decreased in the samples with Salmonella. To investigate the relationship between S. enteritidis infection and inflammatory response, dextran sodium sulfate (DSS) was administered after infection and the results indicate lower survival rate after DSS treatment. In conclusion, we were able to identify the optimal concentration of S. enteritidis to modulate the intestinal mucosal immunity of mice and inflammatory response.

• Korean Journal of Poultry Science
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• v.34 no.1
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• pp.77-83
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• 2007

Poultry products including meat and eggs constitute a major protein source in the American diet and disease-causing pathogens represent major challenges to the poultry industry. More than 95% of pathogens enter the host through the mucosal surfaces of the respiratory, digestive and reproductive tracts and over the past few decades, the two main mechanisms used to control diseases have been the use of vaccines and antibiotics. However, in the poultry industry, there are mounting concerns over the ability of current vaccines to adequately protect against emerging hyper-virulent strains of pathogens and a lack of suitable, cost effective adjuvants. Thorough investigation of the immunogenetic responses involved in host-pathogen interactions will lead to the development of new and effective strategies for improving poultry health, food safety and the economic viability of the US poultry industry. In this paper, I describe the development of immunogenomic and proteomic tools to fundamentally determine and characterize the immunological mechanisms of the avian host to economically significant mucosal pathogens such as Eimeria. Recent completion of poultry genome sequencing and the development of several tissue-specific cDNA libraries in chickens are facilitating the rapid application of functional immunogenomics in the poultry disease research. Furthermore, research involving functional genomics, immunology and bioinformatics is providing novel insights into the processes of disease and immunity to microbial pathogens at mucosal surfaces. In this presentation, a new strategy of global gene expression using avian macrophage (AMM) to characterize the multiple pathways related to the variable immune responses of the host to Eimeria is described. This functional immunogenomics approach will increase current understanding of how mucosal immunity to infectious agents operates, and how it may be enhanced to enable the rational development of new and effective strategies against coccidiosis and other mucosal pathogens.