• IMMUNE NETWORK
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• 제10권6호
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• pp.181-187
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• 2010

Excessive alcohol consumption is one of the critical causative factors leading to alcoholic liver disease (ALD). ALD is characterized by a wide spectrum of liver damage, ranging from simple uncomplicated liver steatosis (fatty liver) to steatohepatitis and liver fibrosis/cirrhosis. It has been believed that the obvious underlying cause for ALD is due to hepatocyte death induced by alcohol itself. However, recent sparkling studies have shown that diverse immune responses contribute to ALD because liver is enriched with numerous immune cells. Especially, a line of evidence has suggested that innate immune cells such as Kupffer cells and natural killer (NK)/NKT cells are significantly involved in the pathogenesis of ALD via production of pro-inflammatory cytokines and other mediators. Indeed, more interestingly, hepatic stellate cells (HSCs), known as a major cell inducing liver steatosis and fibrosis, can be killed by liver NK cells, which could be suppressed by chronic alcohol consumption. In this review, with the view of liver as predominant innate immune organ, we describe the pathogenesis of ALD in which what roles of innate immune cells are and how they are interacting with HSCs.

• 한국가금학회지
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• 제35권3호
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• pp.225-240
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• 2008

Marek's disease virus(MDV) is a highly cell-associated, lymphotropic $\alpha$-herpesvirus that causes paralysis and neoplastic disease in chickens. The disease has been controlled by vaccination which was provided the first evidence for a malignant cancer being controlled by an antiviral vaccine. Marek's disease pathogenesis is complex, involving cytolytic and latent infection of lymphoid cells and oncogenic transformation of $CD4^+$ T cells in susceptible chickens. MDV targets a number of different cell types during its life cycle. Lymphocytes play an essential role, although within them virus production is restricted and only virion are produced. Innate and adaptive immune responses develop in response to infection, but infection of lymphocytes results in immunosuppressive effects. Hence in MDV-infected birds, MDV makes its host more vulnerable to tumour development as well as to other pathogens. All chickens are susceptible to MDV infection, and vaccination is essential to protect the susceptible host from developing clinical disease. Nevertheless, MDV infects and replicates in vaccinated chickens, with the challenge virus being shed from the feather-follicle epithelium. The outcome of infection with MDV depends on a complex interplay of factors involving the MDV pathotype and the host genotype. Host factors that influence the course of MD are predominantly the responses of the innate and adaptive immune systems, and these are modulated by: age at infection and maturity of the immune system; vaccination status; the sex of the host; and various physiological factors.

• Toxicological Research
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• 제30권2호
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• pp.77-81
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• 2014

In contrast to animals, plants do not have a circulatory system as well as mobile immune cells that allow them to protect themselves against pathogens. Instead, plants exclusively depend on the innate immune system to defend against pathogens. As typically observed in the animal innate immunity, plant immune responses are composed of pathogen detection, defense signaling which includes transcriptional reprogramming, and secretion of antimicrobial compounds. Although knowledge on recognition and subsequent signaling of pathogen-derived molecules called elicitors is now expanding, the mechanisms of how these immune molecules are excreted are yet poorly understood. Therefore, current understandings of how plants secrete defense products especially via exocytosis will be discussed in this review.

• 생명과학회지
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• 제29권7호
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• pp.817-823
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• 2019

노화는 광범위한 생리 변화이다. 노화가 진행됨에 따라 면역반응은 쇠퇴하고 조절장애가 나타나는데 이를 포괄적 의미로 immunosenescense라고 정의한다. 내재면역반응과 적응면역 반응 모두의 면역 성분은 노화가 진행됨에 따라 영향을 받아 감염성 질병에 대한 취약성이 증가하게 된다. 노화된 동물 모델과 인간에서 면역 세포의 수와 용해성 면역 인자의 양이 줄어 들었고, 면역체계의 기능이 감소하였고, 구조적인 변형과 퇴화가 나타났다. 또한, 세포 내 신호분자와 같은 내재적 변화도 발견되었다. 최근 노화와 관련된 연구는 급격히 증가하였고, 면역체계 영역을 포함하여 다양한 방향으로 노화현상을 분석하는 진보된 기술들이 개발되고 있다. 이 총설은 면역의 주요 구성 요소의 노화 관련 변화에 대한 광범위한 개요를 제공하고자 하였다.

• Bulletin of the Korean Chemical Society
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• 제35권11호
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• pp.3307-3312
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• 2014

The anti-inflammatory effect of a tubulin inhibitor, N-(5-benzyl-1,3-thiazol-2-yl)-3-(furan-2-yl)prop-2-enamide (1), on innate immune responses remains unclear. Thus, we investigated the effect of 1 on the immune responses mediated by lipopolysaccharide (LPS). The in vitro addition of 1 to dendritic cells and macrophages dose-dependently reduced tumor necrosis factor alpha production elicited by LPS stimulation. Additionally, the stimulation of natural killer (NK) and natural killer T (NKT) cells with 1 resulted in the decrease of interferon gamma ($IFN{\gamma}$) induced by LPS treatment. Moreover, 1 substantially reduced interleukin 12 in dendritic cells (DC) as well as $IFN{\gamma}$ in NKDCs induced by LPS in vitro. Furthermore, the in vivo administration of 1 ameliorated LPS/D-galactosamine-induced endotoxic lethality in mice. Taken together, our results demonstrate for the first time that 1 possesses anti-inflammatory properties, most notably by modulating LPS-induced innate immune responses. Therefore, 1 might have therapeutic potential for the treatment of inflammation-mediated diseases such as sepsis.

• IMMUNE NETWORK
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• 제14권6호
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• pp.307-320
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• 2014

Mycobacterium scrofulaceum is an environmental and slow-growing atypical mycobacterium. Emerging evidence suggests that M. scrofulaceum infection is associated with cervical lymphadenitis in children and pulmonary or systemic infections in immunocompromised adults. However, the nature of host innate immune responses to M. scrofulaceum remains unclear. In this study, we examined the innate immune responses in murine bone marrow-derived macrophages (BMDMs) infected with different M. scrofulaceum strains including ATCC type strains and two clinically isolated strains (rough and smooth types). All three strains resulted in the production of proinflammatory cytokines in BMDMs mediated through toll-like receptor-2 and the adaptor MyD88. Activation of MAPKs (extracellular signal-regulated kinase 1/2, and p38, and c-Jun N-terminal kinase) and nuclear receptor (NF)-${\kappa}B$ together with intracellular reactive oxygen species generation were required for the expression of proinflammatory cytokines in BMDMs. In addition, the rough morphotypes of M. scrofulaceum clinical strains induced higher levels of proinflammatory cytokines, MAPK and NF-${\kappa}B$ activation, and ROS production than other strains. When mice were infected with different M. scrofulaceum strains, those infected with the rough strain showed the greatest hepatosplenomegaly, granulomatous lesions, and immune cell infiltration in the lungs. Notably, the bacterial load was higher in mice infected with rough colonies than in mice infected with ATCC or smooth strains. Collectively, these data indicate that rough M. scrofulaceum induces higher inflammatory responses and virulence than ATCC or smooth strains.

• BMB Reports
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• 제41권4호
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• pp.267-277
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• 2008

Insects mount a robust innate immune response against a wide array of microbial pathogens. The hallmark of the Drosophila humoral immune response is the rapid production of anti-microbial peptides in the fat body and their release into the circulation. Two recognition and signaling cascades regulate expression of these antimicrobial peptide genes. The Toll pathway is activated by fungal and many Gram-positive bacterial infections, whereas the immune deficiency (IMD) pathway responds to Gram-negative bacteria. Recent work has shown that the intensity and duration of the Drosophila immune response is tightly regulated. As in mammals, hyperactivated immune responses are detrimental, and the proper down-modulation of immunity is critical for protective immunity and health. In order to keep the immune response properly modulated, the Toll and IMD pathways are controlled at multiple levels by a series of negative regulators. In this review, we focus on recent advances identifying and characterizing the negative regulators of these pathways.

• IMMUNE NETWORK
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• 제15권1호
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• pp.1-8
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• 2015

Innate immune cells survey antigenic materials beneath our body surfaces and provide a front-line response to internal and external danger signals. Dendritic cells (DCs), a subset of innate immune cells, are critical sentinels that perform multiple roles in immune responses, from acting as principal modulators to priming an adaptive immune response through antigen-specific signaling. In the gut, DCs meet exogenous, non-harmful food antigens as well as vast commensal microbes under steady-state conditions. In other instances, they must combat pathogenic microbes to prevent infections. In this review, we focus on the function of intestinal DCs in maintaining intestinal immune homeostasis. Specifically, we describe how intestinal DCs affect IgA production from B cells and influence the generation of unique subsets of T cell.

• Molecules and Cells
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• 제23권1호
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• pp.1-10
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• 2007

Invading pathogens are recognized by diverse germline-encoded pattern-recognition receptors (PRRs) which are distributed in three different cellular compartments: extracellular, membrane, and cytoplasmic. In mammals, the major extracellular PRRs such as complements may first encounter the invading pathogens and opsonize them for clearance by phagocytosis which is mediated by membrane-associated phagocytic receptors including complement receptors. The major membrane-associated PRRs, Toll-like receptors, recognize diverse pathogens and generate inflammatory signals to coordinate innate immune responses and shape adaptive immune responses. Furthemore, certain membrane-associated PRRs such as Dectin-1 can mediate phagocytosis and also induce inflammatory response. When these more forefront detection systems are avoided by the pathogens, cytoplasmic PRRs may play major roles. Cytoplasmic caspase-recruiting domain (CARD) helicases such as retinoic acid-inducible protein I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5), mediate antiviral immunity by inducing the production of type I interferons. Certain members of nucleotide-binding oligomerization domain (NOD)-like receptors such as NALP3 present in the cytosol form inflammasomes to induce inflammatory responses upon ligand recognition. Thus, diverse families of PRRs coordinately mediate immune responses against diverse types of pathogens.

• Molecules and Cells
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• 제42권1호
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• pp.1-7
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• 2019

Macrophage is an important innate immune cell that not only initiates inflammatory responses, but also functions in tissue repair and anti-inflammatory responses. Regulating macrophage activity is thus critical to maintain immune homeostasis. Tyro3, Axl, and Mer are integral membrane proteins that constitute TAM family of receptor tyrosine kinases (RTKs). Growing evidence indicates that TAM family receptors play an important role in anti-inflammatory responses through modulating the function of macrophages. First, macrophages can recognize apoptotic bodies through interaction between TAM family receptors expressed on macrophages and their ligands attached to apoptotic bodies. Without TAM signaling, macrophages cannot clear up apoptotic cells, leading to broad inflammation due to over-activation of immune cells. Second, TAM signaling can prevent chronic activation of macrophages by attenuating inflammatory pathways through particular pattern recognition receptors and cytokine receptors. Third, TAM signaling can induce autophagy which is an important mechanism to inhibit NLRP3 inflammasome activation in macrophages. Fourth, TAM signaling can inhibit polarization of M1 macrophages. In this review, we will focus on mechanisms involved in how TAM family of RTKs can modulate function of macrophage associated with anti-inflammatory responses described above. We will also discuss several human diseases related to TAM signaling and potential therapeutic strategies of targeting TAM signaling.