• IMMUNE NETWORK
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• 제23권4호
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• pp.31.1-31.18
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• 2023

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

• 생명과학회지
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• 제33권5호
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• pp.429-435
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• 2023

역학 연구에 따르면 임신 중 산모의 감염, 산모의 스트레스, 환경적 위험 요인이 태아의 인지 장애와 관련된 뇌 발달 이상 위험을 증가시키고 정신분열증 및 자폐 스펙트럼 장애에 대한 감수성을 증가시키는 것으로 나타났다. 여러 동물 모델은 모체 면역 활성화(MIA)가 태아와 자손의 비정상적인 뇌 발달 및 행동 결함을 유발하기에 충분하다는 것이 입증되었다. 모체 면역활성화 동물 모델에는 흔히 바이러스 모방 Poly I:C 또는 박테리아 유래물질 LPS 등을 임신한 어미에 도입시킴으로서 모체 면역이 활성화되며, 친염증성 사이토카인이 증가하고 자손의 뇌에서 미세아교세포 활성이 관찰되었다. 미세아교세포는 중추신경계에서 중재 역할을 하는 뇌 상주 면역 세포이다. 미세아교세포는 식균 작용, 시냅스 형성 및 분지, 혈관 신생과 같은 다양한 기능을 담당하는 것으로 알려져 있다. 여러 연구에서 미세아교세포가 모체면역활성화 자손에서 활성화되어 있고, 다양한 사이토카인과의 상호작용을 통해 자손 행동에 영향을 미침이 보고되었다. 또한 신경세포와 별아교세포와의 상호작용을 통해 뇌회로에서도 중요한 역할을 담당한다. 그러나 미세아교세포가 뇌 발달 및 행동 결함에 필수적인지에 대해서는 논란이 있으며 정확한 메커니즘은 아직 알려지지 않다. 따라서 뇌 발달 장애의 잠재적 진단 및 치료를 위해서는 모체면역활성화 동물 모델에서 미세아교세포 기능 연구의 필요성이 더욱 요구되고 있다.

• Journal of Microbiology and Biotechnology
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• 제7권6호
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• pp.423-428
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• 1997

Vibrio vulnificus is a halophilic gram-negative human pathogen, which affects people with underlying liver diseases or a suppressed immune system, often leading to primary septicemia with a mortality rate of higher than 60%. In an effort to develop an oral vaccine against V. vulnificus infection, we prepared a whole cell killed vaccine of V. vulnificus on a large scale and compared the immunogenicity and protective efficacy of the vaccine administered in three formulation forms in rabbits. Since V. vulnificus O-antigen serotypes 1, 2, 3, 4, 5, and 7 account for more than 95% of clinical isolates, we prepared cell lysates from these six serotype strains and mixed in equal amounts for a vaccine. The vaccine was administered to rabbits intramuscularly (i.m.), orally as granules or as enteric-coated granules. In rabbits, all three formulation forms elicited a high level of serum IgG antibody reactive not only to the six strains but also to other O-antigen serotypes 6, 8 and 9, indicating cross-reactivities among the strains. Immunotherapeutic efficacy of the antisera was also evaluated by a passive immunization assay, which revealed that the orally immunized antisera as well as the i.m. immunized antisera was protective against a subsequent lethal challenge of V. vulnificus. These data demonstrate that oral immunization with a V. vulnificus whole cell lysate vaccine induced a systemic immune response and suggest the feasibility of development of this vaccine preparation as an oral vaccine.

• Reproductive and Developmental Biology
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• 제31권1호
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• pp.55-60
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• 2007

Aging causes thymus involution, and genes in thymus play an important role in the development of the immune system. In this study, we compared genes expressed in thymus of neonatal and peripubertal rats using annealing control primers (ACPs)-based GeneFishing polymerase chain reaction (PCR) and semiquantitative reverse transcription (RT)-PCR. We identified 10 differentially expressed genes (DEGs) with 20 ACPs. Of 10 DEGs, bystin-like, collagen type V alpha 1 (COL5A1), and T-cell receptor beta-chain segment 2 (TCRB2) that are related to immune-function were detected in rat thymus. Bystin-like and TCRB2 were up-regulated, while COL5A1 was down-regulated in peripubertal thymus. Semiquantitative RT-PCR confirmed postnatal changes in expression of bystin-like, COL5A1, and TCRB2. These results suggest that bystin-like, COL5A1, and TCRB2 could regulate immune function controlled in thymus as age increases.

• 대한의생명과학회지
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• 제21권2호
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• pp.51-59
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• 2015

A humanized mice (hu-mice) model is extremely valuable to verify human cell activity in vivo condition and is regarded as an important tool in examining multimodal therapies and drug screening in tumor biology. Moreover, hu-mice models that simply received human $CD34^+$ blood cells and tissue transplants are also overwhelmingly useful in immunology and stem cell biology. Because generated hu-mice harboring a human immune system have displayed phenotype of human $CD45^+$ hematopoietic cells and when played partly with functional immune network, it could be used to evaluate human cell properties in vivo. Although the hu-mice model does not completely recapitulate human condition, it is a key methodological factor in studying human hematological malignancies with impaired immune cells. Also, an advanced humanized leukemic mice (hu-leukemic-mice) model has been developed by improving immunodeficient mice. In this review, we briefly described the history of development on immunodeficient SCID strain mice for hu-and hu-leukemic-mice model for immunologic and tumor microenviromental study while inferring the potential benefits of hu-leukemic-mice in cancer biology.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 제2회 추계심포지움
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• pp.61-67
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• 1994

One fundamental problem in developing an AIDS vaccine is antigenic variation of HIV. Despite a substantial induced immune response in gp120-immunized monkeys and humans, high titers of V3-directed type specific neutralizing antibodies may not be sufficient to neutralize continuously emerging new isolates. Several studies analyzing anti-gp120 antibodies in HIV-infected individuals have clearly indicated that most broadly neutralizing antibodies are directed to conformation-dependent epitopes. Therefore, it seems important to evaluate the potential efficacy of candidate gp120 vaccines at inducing such antibodies, that might be potentially protective against multiple HIV strains. One concern in the development of any recombinant protein as a vaccine is its stability when mixed with an adjuvant. This could be a particularly important factor for recombinant gp120, given the conformational nature of its major, broadly neutralizing, epitopes. We hypothesized that gp120 complexed with recombinant CD4 could stabilize the conformation-dependent epitopes and effectively deliver these epitopes to the immune system. In this study, a soluble gp120-CD4 complex in Syntex Adjuvant Formulation was tested in mice to analyze the anti-gp120 antibody response. With the aim of defining the fine specificity and neutalizing activities of the immune response, 17Mabs were generated and characterized. The studies indicate that the gp120-CD4 complex elicits neutralizing anti-gp120 antibodies, most of which are directed to the conformation dependent epitopes.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.7.1-7.14
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• 2018

Dysregulation of long noncoding RNA (lncRNA) expression is linked to the development of various diseases. Recently, an emerging body of evidence has indicated that lncRNAs play important roles in the pathogenesis of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative Colitis (UC). In IBD, lncRNAs have been shown to be involved in diverse processes, including the regulation of intestinal epithelial cell apoptosis, association with lipid metabolism, and cell-cell interactions, thereby enhancing inflammation and the functional regulation of regulatory T cells. In this review, we aim to summarize the current knowledge regarding the role of lncRNAs in IBD and highlight potential avenues for future investigation. We also collate potentially immune-relevant, IBD-associated lncRNAs identified through a built-by association analysis with respect to their neighboring protein-coding genes within IBD-susceptible loci. We further underscore their importance by highlighting their enrichment for various aspects of immune system regulation, including antigen processing/presentation, immune cell proliferation and differentiation, and chronic inflammatory responses. Finally, we summarize the potential of lncRNAs as diagnostic biomarkers in IBD.

• BMB Reports
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• 제56권7호
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• pp.398-403
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• 2023

Natural killer (NK) cells are an essential part of the innate immune system that helps control infections and tumors. Recent studies have shown that Vorinostat, a histone deacetylase (HDAC) inhibitor, can cause significant changes in gene expression and signaling pathways in NK cells. Since gene expression in eukaryotic cells is closely linked to the complex three-dimensional (3D) chromatin architecture, an integrative analysis of the transcriptome, histone profiling, chromatin accessibility, and 3D genome organization is needed to gain a more comprehensive understanding of how Vorinostat impacts transcription regulation of NK cells from a chromatin-based perspective. The results demonstrate that Vorinostat treatment reprograms the enhancer landscapes of the human NK-92 NK cell line while overall 3D genome organization remains largely stable. Moreover, we identified that the Vorinostat-induced RUNX3 acetylation is linked to the increased enhancer activity, leading to elevated expression of immune response-related genes via long-range enhancer-promoter chromatin interactions. In summary, these findings have important implications in the development of new therapies for cancer and immune-related diseases by shedding light on the mechanisms underlying Vorinostat's impact on transcriptional regulation in NK cells within the context of 3D enhancer network.

• IMMUNE NETWORK
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• 제21권3호
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• pp.20.1-20.18
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• 2021

The gut is an important organ with digestive and immune regulatory function which consistently harbors microbiome ecosystem. The gut microbiome cooperates with the host to regulate the development and function of the immune, metabolic, and nervous systems. It can influence disease processes in the gut as well as extra-intestinal organs, including the brain. The gut closely connects with the central nervous system through dynamic bidirectional communication along the gut-brain axis. The connection between gut environment and brain may affect host mood and behaviors. Disruptions in microbial communities have been implicated in several neurological disorders. A link between the gut microbiota and the brain has long been described, but recent studies have started to reveal the underlying mechanism of the impact of the gut microbiota and gut barrier integrity on the brain and behavior. Here, we summarized the gut barrier environment and the 4 main gut-brain axis pathways. We focused on the important function of gut barrier on neurological diseases such as stress responses and ischemic stroke. Finally, we described the impact of representative environmental sensors generated by gut bacteria on acute neurological disease via the gut-brain axis.

• IMMUNE NETWORK
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• 제19권1호
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• pp.2.1-2.13
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• 2019

The enhanced differentiation and activation of osteoclasts (OCs) in the inflammatory arthritis such as rheumatoid arthritis (RA) and gout causes not only local bone erosion, but also systemic osteoporosis, leading to functional disabilities and morbidity. The induction and amplification of NFATc1, a master regulator of OC differentiation, is mainly regulated by receptor activator of NF-κB (RANK) ligand-RANK and calcium signaling which are amplified in the inflammatory milieu, as well as by inflammatory cytokines such as TNFα, IL-1β and IL-6. Moreover, the predominance of CD4⁺ T cell subsets, which varies depending on the condition of inflammatory diseases, can determine the fate of OC differentiation. Anti-citrullinated peptide antibodies which are critical in the pathogenesis of RA can bind to the citrullinated vimentin on the surface of OC precursors, and in turn promote OC differentiation and function via IL-8. In addition to adaptive immunity, the activation of innate immune system including the nucleotide oligomerization domain leucine rich repeat with a pyrin domain 3 inflammasome and TLRs can regulate OC maturation. The emerging perspectives about the diverse and close interactions between the immune cells and OCs in inflammatory milieu can have a significant impact on the future direction of drug development.