• Molecules and Cells
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• 제20권2호
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• pp.173-182
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• 2005

Heat shock protein gp96 is an endoplasmic reticulum chaperone, belonging to the HSP90 family. The function of gp96 as a molecular chaperone was discovered more than 10 years ago, but its importance has been overshadowed by the brilliance of its role in immune responses. It is now clear that gp96 is instrumental in the initiation of both the innate and adaptive immunity. Recently, the roles of gp96 in protein homeostasis, as well as in cell differentiation and development, are beginning to draw more attention due to rapid development in the structural study of HSP90 and some surprising new discoveries from genetic studies of gp96. In this review, we focus on the aspect of gp96 as an ER molecular chaperone in protein maturation, peptide binding and the regulation of its activity.

• 한국어병학회지
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• 제27권1호
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• pp.1-9
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• 2014

저수온기만 넙치에 대량 폐사를 일으키는 바이러스성 출혈성 패혈증을 폐사가 발생하는 $15^{\circ}C$, 폐사가 발생하지 않는 $20^{\circ}C$에서 인공감염시켜 넙치의 면역 유전자 발현 profile을 cDNA microarray 분석하였으며, 특히 저수온기에 폐사가 나타나는 원인을 면역 유전자 발현과 관련시켜 알아보고자 하였다. $15^{\circ}C$, $20^{\circ}C$의 감염 세포구에 공통으로 발현되는 유전자는 MHC class I, IL-8, myeloperoxidase 및 endonuclease G-like 유전자로 모든 세포표면에 존재하여 항원을 제시하거나 호중구 주화성을 자극하는 유전자들이었다. 항원 가공 및 제시, 항체 생성에 관여하는 MHC class II, immunoglobulin (Ig)과 retinoblastoma 등의 유전자는 $20^{\circ}C$에서는 발현이 증가하였으나 $15^{\circ}C$에서는 발현이 감소되었다. 이로부터 폐사가 발생하지 않는 $20^{\circ}C$는 바이러스 감염초기의 항원 제시, MHC class I과 II에 의한 항원제시, apoptosis 및 이후의 항체 생산이 정상적으로 이루어져 폐사가 발생하지 않는 것으로 생각되었다. 그러나 폐사가 발생하는 $15^{\circ}C$에서는 MHC class I매개의 항원 제시와 탐식 작용등의 선천 면역은 이루어지나 macrophage에 의한 MHC class II매개의 항원 제시와 apoptosis저하, 항체 생산 관련 유전자의 발현저하가 관찰되어 초기 macrophage에 의한 항원제시의 실패로 적응 면역이 제대로 활성화되지 않아 폐사가 발생한 것으로 사료된다.

• IMMUNE NETWORK
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• 제14권3호
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• pp.128-137
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• 2014

Respiratory viruses can induce acute respiratory disease. Clinical symptoms and manifestations are dependent on interactions between the virus and host immune system. Dendritic cells (DCs), along with alveolar macrophages, constitute the first line of sentinel cells in the innate immune response against respiratory viral infection. DCs play an essential role in regulating the immune response by bridging innate and adaptive immunity. In the steady state, lung DCs can be subdivided into $CD103^+$ conventional DCs (cDCs), $CD11b^+$ cDCs, and plasmacytoid DCs (pDCs). In the inflammatory state, like a respiratory viral infection, monocyte-derived DCs (moDCs) are recruited to the lung. In inflammatory lung, discrimination between moDCs and $CD11b^+$ DCs in the inflamed lung has been a critical challenge in understanding their role in the antiviral response. In particular, $CD103^+$ cDCs migrate from the intraepithelial base to the draining mediastinal lymph nodes to primarily induce the $CD8^+$ T cell response against the invading virus. Lymphoid $CD8{\alpha}^+$ cDCs, which have a developmental relationship with $CD103^+$ cDCs, also play an important role in viral antigen presentation. Moreover, pDCs have been reported to promote an antiviral response by inducing type I interferon production rather than adaptive immunity. However, the role of these cells in respiratory infections remains unclear. These different DC subsets have functional specialization against respiratory viral infection. Under certain viral infection, contextually controlling the balance of these specialized DC subsets is important for an effective immune response and maintenance of homeostasis.

• Asian-Australasian Journal of Animal Sciences
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• 제32권5호
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• pp.614-628
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• 2019

Objective: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Methods: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and ${\beta}2-microglobulin$ and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines. Conclusion: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ${\beta}2-microglobulin$, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.