• IMMUNE NETWORK
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• 제20권1호
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• pp.6.1-6.20
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• 2020

IL-17 is produced by RAR-related orphan receptor gamma t (RORγt)-expressing cells including Th17 cells, subsets of γδT cells and innate lymphoid cells (ILCs). The biological significance of IL-17-producing cells is well-studied in contexts of inflammation, autoimmunity and host defense against infection. While most of available studies in tumor immunity mainly focused on the role of T-bet-expressing cells, including cytotoxic CD8⁺ T cells and NK cells, and their exhaustion status, the role of IL-17-producing cells remains poorly understood. While IL-17-producing T-cells were shown to be anti-tumorigenic in adoptive T-cell therapy settings, mice deficient in type 17 genes suggest a protumorigenic potential of IL-17-producing cells. This review discusses the features of IL-17-producing cells, of both lymphocytic and myeloid origins, as well as their suggested pro- and/or anti-tumorigenic functions in an organ-dependent context. Potential therapeutic approaches targeting these cells in the tumor microenvironment will also be discussed.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2008년도 International Meeting of the Microbiological Society of Korea
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• pp.23-25
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• 2008

Serum complement proteins comprise an important system that is responsible for several innate and adaptive immune defence mechanisms. There were three well described pathways known to lead to the generation of a C3 convertase, which catalyses the proteolysis of complement component C3, and leads to the formation of C3 opsonins (C3b, iC3b and C3d) that fix to bacteria. A pivotal step in the complement pathway is the assembly of a C3 convertase, which digests the C3 complement component to form microbial-binding C3 fragments recognized by leukocytes. The spleen clears microorganisms from the blood. Individuals lacking this organ are more susceptible to Streptococcus pneumoniae. Innate resistance to S. pneumoniae has previously been shown to involve complement components C3 and C4, however this resistance has only a partial requirement for mediators of these three pathways, such as immunoglobulin, factor B and mannose-binding lectin. Therefore it was likely that spleen and complement system provide resistance against blood-borne S. pneumoniae infection through unknown mechanism. To better understand the mechanisms involved, we studied Specific intracellular adhesion molecule-grabbing nonintegrin (SIGN)-R1. SIGN-R1, is a C-type lectin that is expressed at high levels by spleen marginal-zone macrophages and lymph-node macrophages. SIGN-R1 has previously been shown to be the main receptor for bacterial dextrans, as well as for the capsular pneumococcal polysaccharide (CPS) of S. pneumoniae. We examined the specific role of this receptor in the activation of complement. Using a monoclonal antibody that selectively downregulates SIGN-R1 expression in vivo, we show that in response to S. pneumoniae or CPS, SIGN-R1 mediates the immediate proteolysis of C3 and fixation of C3 opsonins to S. pneumoniae or to marginal-zone macrophages that had taken up CPS. These data indicate that SIGN-R1 is largely responsible for the rapid C3 convertase formation induced by S. pneumoniae in the spleen of mice. Also, we found that SIGN-R1 directly binds C1q and that C3 fixation by SIGN-R1 requires C1q and C4 but not factor B or immunoglobulin. Traditionally C3 convertase can be formed by the classical C1q- and immunoglobulin-dependent pathway, the alternative factor-B-dependent pathway and the soluble mannose-binding lectin pathway. Furthermore Conditional SIGN-R1 knockout mice developed deficits in C3 catabolism when given S. pneumoniae or its capsular polysaccharide intravenously. There were marked reductions in proteolysis of serum C3, deposition of C3 on organisms within SIGN-$R1^+$ spleen macrophages, and formation of C3 ligands. The transmembrane lectin SIGN-R1 therefore contributes to innate resistance by an unusual C3 activation pathway. We propose that in the SIGN-R1 mediated complement activation pathway, after binding to polysaccharide, SIGN-R1 captures C1q. SIGN-R1 can then, in association with several other complement proteins including C4, lead to the formation of a C3 convertase and fixation of C3. Therefore, this new pathway for C3 fixation by SIGN-R1, which is unusual as it is a classical C1q-dependent pathway that does not require immuno globulin, contributes to innate immune resistance to certain encapsulated microorganisms.

• 한국가금학회:학술대회논문집
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• 한국가금학회 2006년도 제23차 정기총회 및 학술발표회
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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.

• 한국수산과학회지
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• 제53권2호
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• pp.191-202
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• 2020

We evaluated the effects of dietary supplementation of phytosterol on the growth, feed utilization, immunity, digestibility, wound healing ability and disease resistance of olive flounder Paralichthys olivaceus. We conducted two consecutive feeding trials at different growth stages of the fish: EXP-1 (68.9 g) and EXP-2 (16.5 g). The experimental diets were supplemented with graded levels of phytosterol (1% ecdysteroid extracted from Achyranthis radix) at 0, 0.025, 0.05, 0.1, 0.2 and 0.4% (designated as Con, PHY0.025, PHY0.05, PHY0.1, PHY0.2 and PHY0.4, respectively). Dietary phytosterol did not significantly affect growth and cholesterol concentration. Feed utilization was higher in fish fed phytosterol-supplemented diets than in fish fed the control diet. Dietary phytosterol increased innate immunity and digestibility of protein and dry matter. Wound healing ability was also increased by the phytosterol supplementation. The survival against Edwardsiella tarda challenge was higher in fish fed low-phytosterol diets than in fish fed the control diet. The optimum dietary level of phytosterol seems to be approximately 0.05%. The results in this study indicate that the phytosterol could be used as a functional supplement in diets to improve feed utilization, immunity, digestibility and wound healing ability of olive flounder.

• Biomolecules & Therapeutics
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• 제24권6호
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• pp.638-649
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• 2016

In the previous study, the rhizome mixture of Anemarrhena asphodeloides and Coptis chinensis (DW2007), improved TNBS-, oxazolone-, or DSS-induced colitis in mice by regulating macrophage activation. Therefore, to understand the effect of DW2007 on the T cell differentiation involved in the adaptive immunity, we measured its effect on both Th17 and Treg cell differentiation in splenocytes, in the lamina propria of mice with DSS-induced colitis (DIC), and in the spleens of mice with collagen-induced arthritis (CIA). Results showed that DW2007 potently inhibited the differentiation of splenocytes into Th17 cells, but increased Treg cell differentiation in vitro. In the colon of wild type and $TLR4^{-/-}$ mice with DIC, DW2007 potently suppressed DSS-induced colon shortening and myeloperoxidase activity. DW2007 also suppressed collagen-induced paw thickening, clinical index, and myeloperoxidase activity in CIA mice. Overall, DW2007 potently suppressed Th17 cell differentiation in mice with CIA and DIC, but increased Treg cell differentiation. Moreover, DW2007 strongly inhibited the expression of TNF-${\alpha}$ and IL-$1{\beta}$, as well as the activation of NF-${\kappa}B$. Based on these findings, DW2007 may ameliorate inflammatory diseases by regulating the innate immunity via the inhibition of macrophage activation and the adaptive immunity via the correction of disturbed Th17/Treg cells.

• 한국수산과학회지
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• 제56권3호
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• pp.300-308
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• 2023

This study aimed to evaluate the utilization of low fish meal (LFM) diet and black soldier fly (BSF) Hermetia illucens meal supplementation in LFM diet as a fish meal (FM) replacer or functional additive for juvenile olive flounder Paralichthys olivaceus. Three LFM diets were prepared to contain 30, 25, and 20% FM, respectively (designated as F30, F25, and F20). Three BSF diets were prepared by adding 2.0, 2.5, and 3.0% BSF in the LFM diets, respectively (designated as F30B2.0, F25B2.5, and F20B3.0). A total of 540 fish (initial mean body weight: 22.3±0.01g) were randomly distributed into 18 tanks (240 L) in triplicate groups and fed the experimental diets twice daily for 12 weeks. Results showed that there were no significant differences in the growth performance, feed utilization and survival among all the groups. Lysozyme activity significantly increased in F30B2.0 and F25B2.5 groups compared to their respective LFM groups. Total immunoglobulin was significantly higher in F30 group than in F20 group. Anti-protease and myeloperoxidase activities were significantly higher in F30B2.0 group than in F20 group. Innate immunity gradually decreased with decreasing FM level in all the groups. BSF supplementation significantly improved immunity compared to their respective LFM diets. Therefore, BSF could be used as an immuno-stimulant supplement in LFM diets for P. olivaceus.

• 한국수산과학회지
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• 제56권6호
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• pp.850-860
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• 2023

The effects of dietary mannan oligosaccharides, Lactobacillus plantarum, Bacillus subtilis, and Bacillus licheniformis supplementation on hybrid grouper Epinephelus akaara ♀×Epinephelus lanceolatus ♂ were evaluated. The fish were fed a basal diet and five other diets consisting of 0.6% mannan oligosaccharides, L. plantarum, B. subtilis, and B. licheniformis and mixture of each 0.15% prebiotic and all the probiotics (designated as MOS, LP, BS, BL, and SYN) for 56 days. Growth performance and feed utilization showed no significant differences among all experimental groups. Lipid level of whole-body was significantly high in MOS and BL groups. Plasma aspartate aminotransferase was significantly low in BL and SYN groups. Nitro-blue tetrazolium, lysozyme and anti-protease, and glutathione peroxidase in BS, SYN, and all probiotic groups, respectively, were significantly high. Intestinal Vibrio bacteria was significantly low in all probiotic and SYN groups. Gene expression of interleukin-1β and interleukin-10 in SYN group; transforming growth factor β2 in MOS and BS groups, toll-like receptor 2-2 in BS and BL groups; and C-type lectin in MOS, LP and SYN groups were significantly upregulated. Our findings indicate that mannan oligosaccharides, L. plantarum, B. subtilis, and B. licheniformis could improve innate immunity, antioxidant capacity, anti-inflammation, and intestinal microbiota of hybrid grouper.

• 한국수산과학회지
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• 제57권3호
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• pp.239-252
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• 2024

Recombination activating genes (RAGs) play a crucial role in initiating V(D)J recombination, which is essential for developing adaptive immunity in vertebrates. In this study, we cloned and characterized RAG1/2 cDNA from the marine medaka Oryzias dancena (OdRAG1/2) and investigated their mRNA expression patterns during ontogenetic developmental stages. The OdRAG1 and OdRAG2 cDNA contained open reading frames (ORFs) encoding proteins containing 1,078 and 531 amino acids, respectively. Multiple sequence alignment and phylogenetic analysis revealed that OdRAG1 and OdRAG2 are highly conserved with their corresponding orthologs, featuring distinct core and non-core regions. Notably, expression analysis showed that, in contrast to other fish RAGs studied, OdRAG1/2 expression peaked at 0 days post-hatching (DPH). Additionally, for the expression of T and B cell differentiation markers, CD3γ and CD20, also peaked at 0 DPH. Collectively, adaptive immunity in O. dancena potentially begins during embryonic development, which is critical for V(D)J recombination and essential immune component development, suggesting the early ontogenetic stage interactions between innate and adaptive immunity.

• 생명과학회지
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• 제32권1호
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• pp.36-43
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• 2022

점막면역체계는 병원체에 대항하여 정밀하게 설계된 생물체의 방어체계로 그 중 위장관은 최전방에서 가장 중요한 기능을 하는 기관이다. 숙주 감염을 일으키는 병원성 미생물 가운데 식중독을 유발하는 살모넬라는 구강경로로 체내로 들어와 파이어판을 통해서 침입한다. 다양한 혈청형의 살모넬라 균주는 여러 톨유사수용체의 리간드를 통해서 숙주의 선천면역을 자극하지만, 숙주 특이성과 병원성에 따라 장내 점막에서 다양한 후천면역반응을 유도하기도 한다. 우리는 살모넬라 균주 중 비교적 연구가 덜 되어있는 S. enteritidis에 의해 감염되었을 때 장 내에서 일어나는 면역반응을 연구하였다. 우선 마우스에 처리할 적정 농도의 살모넬라 농도를 정하기 위해 살모넬라의 농도를 다르게 하여 실험을 진행하였고 고농도의 살모넬라 처리군에서 더 낮은 생존율과 높은 몸무게 감소율을 관찰하였다. 반수치사량의 반에 해당하는 농도의 살모넬라를 마우스에 감염시켰을 때 장 내 수지상세포와 T 세포에 유의적인 차이가 없는 것을 확인하였다. 하지만 동일한 조건의 마우스에서 회장조직을 염색했을 때 뮤신 분비의 증가와 술잔세포의 감소를 확인할 수 있었다. 또한 밀착연접단백질 유전자의 상대적인 발현량을 분석하였고 살모넬라 처리군에서 Claudin의 유의적인 감소를 확인할 수 있었다. 이어 살모넬라 감염 후 DSS를 처리한 실험에서 살모넬라 처리군에서 생존율이 낮아짐을 확인하여 S. enteritidis가 염증반응을 악화시킨다는 것을 알 수 있었다.

• Journal of Microbiology and Biotechnology
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• 제29권12호
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• pp.1873-1881
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• 2019

The innate immune response serves as a first-line-of-defense mechanism for a host against viral infection. Viruses must therefore subvert this anti-viral response in order to establish an efficient life cycle. In line with this fact, Kaposi's sarcoma-associated herpesvirus (KSHV) encodes numerous genes that function as immunomodulatory proteins to antagonize the host immune system. One such mechanism through which KSHV evades the host immunity is by encoding a viral homolog of cellular interferon (IFN) regulatory factors (IRFs), known as vIRFs. Herein, we summarize recent advances in the study of the immunomodulatory strategies of KSHV vIRFs and their effects on KSHV-associated pathogenesis.