• IMMUNE NETWORK
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• v.10 no.6
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• pp.198-205
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• 2010

Background: A crucial limitation of DNA vaccines is its weak immunogenicity, especially in terms of eliciting antibody responses in non-human primates or humans; therefore, it is essential to enhance immune responses to vaccination for the development of successful DNA vaccines for humans. Methods: Here, we approached this issue by evaluating interleukin-7 (IL-7) as a genetic adjuvant in cynomolgus monkeys immunized with multigenic HCV DNA vaccine. Results: Codelivery of human IL-7 (hIL-7)-encoding DNA appeared to increase DNA vaccine-induced antibody responses specific for HCV E2 protein, which plays a critical role in protecting from HCV infection. HCV-specific T cell responses were also significantly enhanced by codelivery of hIL-7 DNA. Interestingly, the augmentation of T cell responses by codelivery of hIL-7 DNA was shown to be due to the enhancement of both the breadth and magnitude of immune responses against dominant and subdominant epitopes. Conclusion: Taken together, these findings suggest that the hIL-7-expressing plasmid serves as a promising vaccine adjuvant capable of eliciting enhanced vaccine-induced antibody and broad T cell responses.

• Journal of Life Science
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• v.29 no.7
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• pp.817-823
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• 2019

Immune system provides defense integrity of body against external invaders. In order to accomplish the important defending role immune system is composed of many different components which are regenerated continuously during lifespan. The key components are professional killing cells such as macrophage, neutrophil, natural killer cell, and cytotoxic T cell and professional blocking molecule, antibody, which is produced by plasma cell, the terminal differentiated B cell. Immune response is orchestrated harmoniously by all these components mediated through antigen presenting cells such as dendritic cells. Immune responses can be divided into two ways: innate immune response and adaptive immune response depending on induction mechanism. Aging is a broad spectrum of physiological changes. Likewise other physiological changes, the immune components and responses are wane as aging is progressing. Immune responses become decline and dysregulating, which is called immunosenescense. Immune components of both innate and adaptive immune response are affected as aging progresses leading to increased vulnerability to infectious diseases. Numbers of immune cells and amounts of soluble immune factors were decreased in aged animal models and human and also functional and structural alterations in immune system were reduced and declined. Cellular intrinsic changes were discovered as well. Recent researches focusing on aging have been enormously growing. Many advanced tools were developed to bisect aging process in multi-directions including immune system area. This review will provide a broad overview of aging-associated changes of key components of immunity.

• 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.

• Journal of Microbiology and Biotechnology
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• v.7 no.1
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• pp.56-61
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• 1997

A strain producing immunosuppressive substances was isolated from a soil in Cheju island. By morphological, cultural, and physiological studies, the strain was identified as Streptomyces lydicus MCY-524. Cultured broth was purified by silica gel, sephadex LH-20 and preparative HPLC and gave two immunosuppressive compounds, MCH-22 and MCH-32. They dramatically suppressed the B cell activation with lipopolysaccharide, T cell activation by mixed lymphocyte response, and primary T-dependent antibody response at a final concentration of 1 ${\mu}g$/ml. They also markedly suppressed the proliferation of lymphocytes induced by lipopolysaccharide, pokeweed mitogen, and concanavaline A at the same concentration. Their suppressive activities, which were comparable to those of cyclosporin A, suggested that they were potent and broad immunotoxic agents on the immune functions of murine lymphocytes.

• BMB Reports
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• v.57 no.7
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• pp.318-323
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• 2024

Regulation of cell fate and lung cell differentiation is associated with Aminoacyl-tRNA synthetases (ARS)-interacting multifunctional protein 2 (AIMP2), which acts as a non-enzymatic component required for the multi-tRNA synthetase complex. In response to DNA damage, a component of AIMP2 separates from the multi-tRNA synthetase complex, binds to p53, and prevents its degradation by MDM2, inducing apoptosis. Additionally, AIMP2 reduces proliferation in TGF-β and Wnt pathways, while enhancing apoptotic signaling induced by tumor necrosis factor-α. Given the crucial role of these pathways in tumorigenesis, AIMP2 is expected to function as a broad-spectrum tumor suppressor. The full-length AIMP2 transcript consists of four exons, with a small section of the pre-mRNA undergoing alternative splicing to produce a variant (AIMP2-DX2) lacking the second exon. AIMP2-DX2 binds to FBP, TRAF2, and p53 similarly to AIMP2, but competes with AIMP2 for binding to these target proteins, thereby impairing its tumor-suppressive activity. AIMP2-DX2 is specifically expressed in a diverse range of cancer cells, including breast cancer, liver cancer, bone cancer, and stomach cancer. There is growing interest in AIMP2-DX2 as a promising biomarker for prognosis and diagnosis, with AIMP2-DX2 inhibition attracting significant interest as a potentially effective therapeutic approach for the treatment of lung, ovarian, prostate, and nasopharyngeal cancers.

• Journal of Convergence Korean Medicine
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• v.6 no.1
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• pp.29-36
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• 2024

Objectives: Psoriasis is a common chronic inflammatory skin disease characterized by keratinocyte hyperproliferation and an excessive inflammatory response. Agents that can attenuate keratinocyte hyperproliferation and excessive inflammatory responses are considered potentially useful for the treatment of psoriasis. Daehwangmokdanpitang (DHMDPT) exhibits a broad range of bioactivities, including anti-proliferative and anti-inflammatory effects. This study aims to evaluate the anti-psoriatic potential of DHMDPT in vitro. Methods: HaCaT keratinocytes were stimulated with a mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish an in vitro psoriatic keratinocyte model. Cell viability was measured using the MTT assay. Quantitative real-time PCR (qRT-PCR) was performed to measure the mRNA levels of the hyperproliferative marker gene keratin 6 (KRT6) and inflammatory factors such as IL-6, TNF-α, and IL-23A. Additionally, chemokines including CCL5, CCL2, CCL20, and CXCL1 were measured by qRT-PCR. Results: DHMDPT attenuated M5-induced hyperproliferation, as indicated by a reduction in KRT6 expression in HaCaT keratinocytes. M5 stimulation significantly upregulated the mRNA levels of IL-6, TNF-α, and IL-23A. However, DHMDPT treatment attenuated the upregulation of IL-6 but not TNF-α or IL-23A. Additionally, DHMDPT inhibited the expression of CCL5, CCL2, and CXCL1, but not CCL20. Conclusion: DHMDPT effectively attenuated the M5-induced proliferation and inflammatory response in HaCaT keratinocytes. Therefore, DHMDPT could be an attractive candidate for future development as an anti-psoriatic agent.

• Molecules and Cells
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• v.46 no.3
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• pp.142-152
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• 2023

Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the cellular antioxidant response, allowing adaptation and survival under conditions of oxidative, electrophilic and inflammatory stress, and has a role in metabolism, inflammation and immunity. Activation of Nrf2 provides broad and long-lasting cytoprotection, and is often hijacked by cancer cells, allowing their survival under unfavorable conditions. Moreover, Nrf2 activation in established human tumors is associated with resistance to chemo-, radio-, and immunotherapies. In addition to cancer cells, Nrf2 activation can also occur in tumor-associated macrophages (TAMs) and facilitate an anti-inflammatory, immunosuppressive tumor immune microenvironment (TIME). Several cancer cell-derived metabolites, such as itaconate, L-kynurenine, lactic acid and hyaluronic acid, play an important role in modulating the TIME and tumor-TAMs crosstalk, and have been shown to activate Nrf2. The effects of Nrf2 in TIME are context-depended, and involve multiple mechanisms, including suppression of proinflammatory cytokines, increased expression of programmed cell death ligand 1 (PD-L1), macrophage colony-stimulating factor (M-CSF) and kynureninase, accelerated catabolism of cytotoxic labile heme, and facilitating the metabolic adaptation of TAMs. This understanding presents both challenges and opportunities for strategic targeting of Nrf2 in cancer.