인간 내생 레트로바이러스(Human Endogenous Retrovirus, HERV)의 염증반응 조절 기작

고은지(Eun-Ji Ko),차희재(Hee-Jae Cha) 한국생명과학회 2021 생명과학회지 Vol.31 No.8

인간 내생 레트로바이러스(Human Endogenous Restrovirus, HERV)는 수백만년전 인간의 유전체에 삽입되었으며 이후 오랜 세월을 거치며 재조합, 결실 및 돌연변이 등 여러 원인에 의해 더 이상 활성화된 바이러스로 역할을 하지 못하고 감염되지 않는다. 하지만 HERV는 최근 연구들은 HERV 유래 인자들이 실제 생리현상 및 암을 비롯한 특정 질환에 관여 하고 있다는 것을 보여 주었다. HERV와 관련된 여러가지 생리 현상 중 염증반응에 초점을 맞추어 고찰해 볼 필요가 있다. HERV는 류마티스, 다발성 경화증, 근위축성 측삭경화증, 쇼그렌 증후군 같은 자가면역질환을 비롯한 여러 염증질환에 직접적으로 관여하는 것으로 보고 되고 있다. HERV의 염증 조절 기작으로는 HERV 유래 인자들이 비특이적 선천성 면역과정을 유발할 가능성과 HERV 유래의 RNA와 단백질이 특정 수용체를 통해 선택적 신호전달기작을 유발할 가능성을 고려 할 수 있다. 하지만 어떠한 방식으로 잠재되어 있던 HERV가 염증반응에서 활성화 되는지 또한 HERV와 관여된 인자들과 신호기작들이 어떠한 것들이 있는지 등 HERV의 인자들이 염증반응을 조절하는 기작에는 아직 많은 것들이 밝혀지지 않아 질병 발병에 대한 연구에 어려움이 있는 실정이다. 본 리뷰에서는 HERV 관련 자가 면역질환을 소개하고 염증반응 조절 기작에 관한 HERV의 분자수준에서의 작용 메커니즘을 제안 하고자 한다. Human endogenous retroviruses (HERVs) were inserted into the human genome millions of years ago but they are currently inactive and non-infectious due to recombinations, deletions, and mutations after insertion into the host genome. Nonetheless, recent studies have shown that HERV-derived elements are actually involved in physiological phenomena and certain diseases including cancers. Among the various physiological phenomena related to HERV-derived elements, it is necessary to focus on inflammatory response. HERV-derived elements have been reported to be directly involved in various inflammatory diseases, including autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, amyotrophic lateral sclerosis, and Sjogren’s syndrome. As a mechanism for regulating inflammation through HERV-derived elements, the possibility that HERV-derived elements may cause nonspecific innate immune processes and that HERV-derived RNA or proteins may cause selective signaling mechanisms through specific receptors can be considered. However, the mechanism through which HERV-derived elements regulate inflammatory response, such as how silent HERV elements are activated in inflammatory response and what factors and signaling mechanisms are involved in HERV-derived elements, have not been identified to date, making it difficult to study the onset of HERV-related inflammatory disease. In this review, we introduce HERV-related autoimmune diseases and propose the mechanisms of HERV-derived elements at the molecular level of HERV in inflammatory response.

The Roles of Human Endogenous Retroviruses (HERVs) in Inflammation

고은지,차희재 고신대학교(의대) 고신대학교 의과대학 학술지 2021 고신대학교 의과대학 학술지 Vol.36 No.2

Human endogenous retroviruses (HERVs) are ancient, currently inactive, and non-infectious due to recombination, deletions, and mutations in the host genome. However, HERV-derived elements are involved in physiological phenomena including inflammatory response. In recent studies, HERV-derived elements were involved directly in various inflammatory diseases including autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Sjogren’s syndrome. Regarding the involvement of HERV-derived elements in inflammation, two possible mechanisms have been proposed. First, HERV-derived elements cause nonspecific innate immune processes. Second, HERV-derived RNA or proteins might stimulate selective signaling mechanisms. However, it is unknown how silent HERV elements are activated in the inflammatory response and what factors and signaling mechanisms are involved with HERV-derived elements. In this review, we introduce HERV-related autoimmune diseases and propose the possible action mechanisms of HERV-derived elements in the inflammatory response at the molecular level.

Histone deacetylase 6 in health and disease.

Seidel, Carole,Schnekenburger, Michael,Dicato, Mario,Diederich, Marc Future Medicine 2015 Epigenomics Vol.7 No.1

<P>Histone deacetylase (HDAC)6 is a member of the class IIb HDAC family. This enzyme is zinc-dependent and mainly localized in the cytoplasm. HDAC6 is a unique isoenzyme with two functional catalytic domains and specific physiological roles. Indeed, HDAC6 deacetylates various substrates including 관-tubulin and HSP90관, and is involved in protein trafficking and degradation, cell shape and migration. Consequently, deregulation of HDAC6 activity was associated to a variety of diseases including cancer, neurodegenerative diseases and pathological autoimmune response. Therefore, HDAC6 represents an interesting potential therapeutic target. In this review, we discuss structural features of this histone deacetylase, regulation of its expression and activity, biological functions, implication in human disease initiation and progression. Finally will describe novel and selective HDAC6 inhibitors.</P>

쉐그렌증후군과 항 갑상선 항체의 상승을 동반한 비혈관염 자가면역 염증성 뇌병증 1예

이성준,손성연,임태성,문소영 대한치매학회 2011 Dementia and Neurocognitive Disorders Vol.10 No.3

Background: Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM) is known to be one of the causes of potentially reversible dementia. NAIM can be accompanied by various autoimmune diseases. Methods: A 65 year-old woman had been treated with stable bipolar disorder and presented with rapid cognitive decline, visual hallucination and myoclonus. Anti-thyroid antibodies were elevated. Her symptoms were responsive to steroid therapy. Her diagnostic evaluation also revealed Sjögren’s syndrome. Although her symptoms recovered, a manic episode reappeared and was responsive to psychiatric treatment. Conclusions: Patients presenting with rapidly progressive dementia should be thoroughly evaluated for the diagnosis of NAIM, a potentially treatable form of dementia, and the possible various underlying autoimmune etiologies.

Retinal transcriptome profiling identifies novel candidate genes associated with visual impairment in a mouse model of multiple sclerosis

홍성무,Poornima D. E. Weerasinghe-Mudiyanselage,강소희,문창종,신태균 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1

Visual impairment is occasionally observed in multiple sclerosis (MS) and its animal model,experimental autoimmune encephalomyelitis (EAE). Although uveitis and optic neuritis havebeen reported in MS and EAE, the precise mechanisms underlying the pathogenesis of thesevisual impairments remain poorly understood. This study aims to identify differentiallyexpressed genes (DEGs) in the retinas of mice with EAE to identify genes that may beimplicated in EAE-induced visual impairment. Fourteen adult mice were injected with myelinoligodendrocyte glycoprotein35–55 to induce the EAE model. Transcriptomes of retinas with EAEwere analyzed by RNA-sequencing. Gene expression analysis revealed 347 DEGs in the retinas ofmice with EAE: 345 were upregulated, and 2 were downregulated (adjusted p-value < 0.05 andabsolute log2 fold change > 1). Gene ontology (GO) analysis showed that the upregulated genesin the retinas of mice with EAE were primarily related to immune responses, responses toexternal biotic stimuli, defense responses, and leukocyte-mediated immunity in the GObiological process. The expression of six upregulated hub genes (c1qb, ctss, itgam, itgb2, syk,and tyrobp) from the STRING analysis and the two significantly downregulated DEGs (hapln1and ndst4) were validated by reverse transcription-quantitative polymerase chain reaction. Inaddition, gene set enrichment analysis showed that the negatively enriched gene sets in EAEaffectedretinas were associated with the neuronal system and phototransduction cascade. Thisstudy provides novel molecular evidence for visual impairments in EAE and indicates directionsfor further research to elucidate the mechanisms of these visual impairments in MS.

단백질 항원의 경구투여에 의해 유도되는 면역반응 및 자가면역질환 치료법으로서의 경구관용

김순미,박희옥 京畿專門大學 1995 京畿專門大學 論文集 Vol.- No.23

Therapeutic Potential of Regulating Mitochondrial RNAs

Yoosik KIM 한국생물공학회 2022 한국생물공학회 학술대회 Vol.2022 No.4

Psychotic Symptoms of Hashimoto’s Encephalopathy

Monisha K Savarimuthu,Sherab Tsheringla,Priya Mammen 대한소아청소년정신의학회 2019 소아청소년정신의학 Vol.30 No.1

Stabilization of Mitochondrial Double-stranded RNAs by SLIRP Amplifies the Antiviral Signaling and Promotes Interferon Response

Doyeong KU,Namseok LEE,Yong-ki LEE,Sujin KIM,Raisa KHARBASH,Yoosik KIM 한국생물공학회 2023 한국생물공학회 학술대회 Vol.2023 No.4