• 제목/요약/키워드: Autoimmunity

검색결과 107건 처리시간 0.032초

Evidence for VH Gene Replacement in Human Fetal B Cells

  • Lee, Jisoo;Cho, Young Joo;Lipsky, Peter E.
    • IMMUNE NETWORK
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    • 제2권2호
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    • pp.79-85
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    • 2002
  • Background: In contrast to evidences of Ig H chain receptor editing in transformed cell lines and transgenic mouse models, there has been no direct evidence that this phenomenon occurs in human developing B cells. Methods: $V_HDJ_H$ rearrangements were obtained from genomic DNA of individual $IgM^-$ B cells from liver and $IgM^+B$ cells from bone marrow of 18 wk of gestation human fetus by PCR amplification and direct sequencing. Results: We found three examples of H chain receptor editing from $IgM^+$ and $IgM^-human$ fetal B cells. Two types of $V_H$ replacements were identified. The first involved $V_H$ hybrid formation, in which part of a $V_H$ gene from the initial VDJ rearrangement is replaced by part of an upstream $V_H$ gene at the site of cryptic RSS. The second involved a gene conversion like replacement of CDR2, in which another $V_H$ gene donated a portion of its CDR2 sequence to the initial VDJ rearrangement. Conclusion: These data provide evidence of receptor editing at the H chain loci in developing human B cells, and also the first evidence of a gene conversion event in human Ig genes.

Dyslipidemia promotes germinal center reactions via IL-27

  • Ryu, Heeju;Chung, Yeonseok
    • BMB Reports
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    • 제51권8호
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    • pp.371-372
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    • 2018
  • Cardiovascular disease such as atherosclerosis is caused by imbalanced lipid metabolism and represents a leading cause of death worldwide. Epidemiological studies show that patients with systemic autoimmune diseases exhibit a higher incidence of atherosclerosis. Conversely, hyperlipidemia has been known to accelerate the incidence of autoimmune diseases in humans and in animal models. However, there is a considerable gap in our understanding of how atherosclerosis impacts the development of the autoimmunity in humans, and vice versa. The atherosclerosis-related autoimmune diseases include psoriasis, rheumatoid arthritis, systemic lupus erythematosus (SLE) and diabetes mellitus. By using animal models of atherosclerosis and SLE, we have recently demonstrated that hyperlipidemia significantly accelerates the development of autoantibodies, by inducing autoimmune follicular helper T ($T_{FH}$) cells. Mechanistic studies have identified that hyperlipidemia induces IL-27 production in a TLR4-dependent manner, likely via downregulating LXR expression in dendritic cells. In this case, mice lacking IL-27 do not develop enhanced antibody responses. Thus it is noted that these findings propose a mechanistic insight responsible for the tight association between cardiovascular diseases and SLE in humans.

Potential Role of Bacterial Infection in Autoimmune Diseases: A New Aspect of Molecular Mimicry

  • Alam, Jehan;Kim, Yong Chul;Choi, Youngnim
    • IMMUNE NETWORK
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    • 제14권1호
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    • pp.7-13
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    • 2014
  • Molecular mimicry is an attractive mechanism for triggering autoimmunity. In this review, we explore the potential role of evolutionary conserved bacterial proteins in the production of autoantibodies with focus on granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA). Seven autoantigens characterized in GPA and RA were BLASTed against a bacterial protein database. Of the seven autoantigens, proteinase 3, type II collagen, binding immunoglobulin protein, glucose-6-phosphate isomerase, ${\alpha}$-enolase, and heterogeneous nuclear ribonuclear protein have well-conserved bacterial orthologs. Importantly, those bacterial orthologs are also found in human-associated bacteria. The wide distribution of the highly conserved stress proteins or enzymes among the members of the normal flora and common infectious microorganisms raises a new question on how cross-reactive autoantibodies are not produced during the immune response to these bacteria in most healthy people. Understanding the mechanisms that deselect auto-reactive B cell clones during the germinal center reaction to homologous foreign antigens may provide a novel strategy to treat autoimmune diseases.

Baicalin Ameliorates Dysimmunoregulation in Pristane-Induced Lupus Mice: Production of IL-6 and $PGE_2$ and Activation of T cells

  • Chae, Byeong-Suk
    • Natural Product Sciences
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    • 제17권4호
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    • pp.354-362
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    • 2011
  • Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by abnormalities in T cell immunoregulation and hyperreactivity of B cells, leading to autoantibody production and multiorgan injuries. We investigated the effect of baicalin on aberrant immunoregulation in pristane-induced lupus mice. Mice received i.p. a single injection of 0.5 ml of pristane or PBS, and approximately 3 months later, were used as a pristane-induced lupus model or healthy controls. The pristane-induced lupus mice and healthy mice were randomly divided into three groups: healthy mouse group (healthy control), pristane-primed lupus control group (lupus control), and baicalin (BAC)-treated pristane-primed lupus mouse group (BAC-treated lupus). The pristane-induced lupus mice and healthy mice were administrated orally with BAC 50 mg/kg or PBS once in a day for 10 ds. These results demonstrated that levels of serum IL-6, LPS-induced production of IL-6, $PGE_2$ and NO by macrophages, $PGE_2$-stimulated production of IL-6 by macrophages and IFN-${\gamma}$ by thymocytes, and an overexpression of splenic NKT cells and CD69+CD4+ T cells were downregulated in BAC-treated lupus compared to lupus control, while reduced apoptosis of splenic CD4+ T cells were upregulated. Therefore, these findings suggest that BAC may attenuate autoimmunity and disease activity in lupus via downregulation of aberrant activation of T cells and inhibition of overproduction of IL-6 and $PGE_2$ in pristane-induced lupus mice.

내인성 레트로바이러스의 발현과 질병 (Expression of Endogenous Retroviruses and Disease)

  • 이재영
    • 미생물학회지
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    • 제43권4호
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    • pp.237-242
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    • 2007
  • 레트로바이러스(Retrovirus; RV)의 독특한 특징 중 하나는 프로바이러스의 상태로 숙주세포의 염색체에 삽입되어 숙주세포 유전자의 일부분으로서 다른 숙주세포 유전자들과 함께 다음세대로 유전된다는 것이다. 이러한 독특한 형태의 RV를 내인성 RV (endogenous RV; ERV)라고 하는데, 여러 종류의 내 외적신호에 의해 그자신의 유전자뿐만 아니라 인근한 숙주유전자의 발현에 변화가 일어난다. 사람과 쥐에서는 각각 HERV (Human ERV)와 MuERV (Murine ERV)가 세포 속에 존재하여 이들의 발현 변화가 숙주 생물체에 주로 해롭게 작용하여 질병을 일으키게 된다. 이들 ERV는 생체분자, 세포물질들이 관여하는 기작을 통해 암과 자가면역 반응과 같은 질병을 일으키는데, 이에 수반하여 많은 병리생리적 변화를 가져온다. HERV와 관련된 질병을 앓고 있는 환자들을 위해서는 이러한 질병을 이해하고, 이를 바탕으로 치료요법을 개발하기 위해 여러 단계의 대책들이 고려되어야 한다.

근 경련과 전신성 탈모증을 보인 Satoyoshi 증후군 1례 (A Case of Satoyoshi Syndrome Presented with Progressive Muscular Spasm and Alopecia)

  • 손경란;국진화;김병주;김성진;마재숙
    • Clinical and Experimental Pediatrics
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    • 제45권9호
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    • pp.1165-1169
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    • 2002
  • 저자들은 근 경련에 의한 근육통과 전신성 탈모증으로 내원하여 Satoyoshi 증후군으로 진단된 1례를 경험하였기에 보고하는 바이며, 근 경련에 탈모증이 동반된 환아의 진단에 있어 Satoyoshi 증후군을 고려해야 할 것으로 사료된다.

3D 영상 기반에서 시각 및 청각 뇌 자극을 이용한 가상현실 건강치유기법에 관한 연구 (A study on Health healing method for incite to the brain of the part of the visual nerve and auditory)

  • 정양권
    • 한국전자통신학회논문지
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    • 제3권4호
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    • pp.233-239
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    • 2008
  • 본 연구는 시각과 청각을 자극하여 자가 면역 효과를 극대화하여 자가 치유 능력이 가능하도록 지원해 주는 시스템 구현에 관한 연구이다. 유사한 연구 중 후각을 자극하는 방법으로 향기를 이용하여 행동, 감정, 정신들을 지배하는 뇌가 여러 모의 정신적인 불균형을 바로 잡아주는 것이 가능함을 인정하고 있듯이, 본 연구는 시각과 청각을 통하여 이용자로 하여금 가상현실에서 사용자를 표시 창에 표시하여 정신과 감정들을 뇌로 하여금 제어하는 과정을 통해 원활하게 기(氣)와 혈(穴)의 흐름을 유도함과 동시에 면역 효과에 가장 이로운 호르몬을 생성하게 하는 시스템에 관한 연구와 타당성을 연구해 보고자 본 시스템을 개발하고 사용 전 후 의 대상자의 알파파를 중심으로 변화 및 영향을 알아보고자 하였다.

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Appearance of osteoporosis in rat experimental autoimmune encephalomyelitis

  • Ahn, Meejung;Kang, Sohi;Park, Channam;Kim, Jeongtae;Jung, Kyungsook;Yang, Miyoung;Kim, Sung-Ho;Moon, Changjong;Shin, Taekyun
    • 대한수의학회지
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    • 제56권2호
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    • pp.117-120
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    • 2016
  • Experimental autoimmune encephalomyelitis (EAE) in Lewis rats is characterized by transient paralysis followed by recovery. To evaluate whether transient paralysis in EAE affects bone density, tibiae of EAE rats were morphologically investigated using micro-computed tomography and histology. The parameters of bone health were significantly reduced at the peak stage of EAE rats relative to those of controls (p < 0.05). The reduction of bone density was found to remain unchanged, even in the recovery stage. Collectively, the present data suggest that osteoporosis occurs in paralytic rats with monophasic EAE, possibly through the disuse of hindlimbs and/or autoimmune inflammation.

Inhibition of Interleukin-12 Production in Mouse Macrophages via Decreased Nuclear $Factor-\kappaB$ DNA Binding Activity by Myricetin, a Naturally Occurring Flavonoid

  • Kang Bok Yun;Kim Seung Hyun;Cho Dae Ho;Kim Tae Sung
    • Archives of Pharmacal Research
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    • 제28권3호
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    • pp.274-279
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    • 2005
  • Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy for preventing the development and progression of disease in experimental models of autoimmunity. In this study, the effects of myricetin, a naturally occurring flavonoid present in fruits, vegetables and medicinal herbs, on the production of IL-12 were investigated in mouse macrophages stimulated with lipopolysaccharide (LPS). Myricetin significantly inhibited the LPS­induced IL-12 production from both primary macrophages and the RAW264.7 monocytic cell-line in a dose-dependent manner. The effect of myricetin on IL-12 gene promoter activation was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs. The repressive effect was mapped to a region in the IL-12 gene promoter containing a binding site for NF-${\kappa}B$. Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF-${\kappa}B$ site, which significantly decreased upon addition of myricetin, indicating that myricetin inhibited IL-12 production in LPS-activated macrophages via the down­regulation of NF-KB binding activity.

프리스탄 유도한 루푸스 생쥐에서 사이토카인 Ex vivo 생산에 미치는 Baicalin의 효과 (Effect of Baicalin on the Ex vivo Production of Cytokines in Pristane-Induced Lupus Mice)

  • 채병숙
    • 약학회지
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    • 제60권1호
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    • pp.21-28
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    • 2016
  • Systemic lupus erythematosus (SLE) is characterized by dysregulatory production of proinflammatory cytokines and helper T (Th) cytokine-dependent autoantibody production. This study aims to investigate the protective effect of baicalin on the dysregulatory production of proinflammatory cytokines and Th cytokines in pristane-induced lupus mice. Mice were received i.p. a single injection of 0.5 ml of pristane, and then, later about 3 months, were used as a pristane-induced lupus model. The pristane-induced lupus mice were administrated orally with baicalin 50 mg/kg once in a day for 10 days. Immune cells obtained from the pristane-primed lupus control group (lupus control) and baicalin-treated pristaneprimed lupus mouse group (BAC lupus) were cultured for 24 h or 36 h with/without mitogens. These results demonstrated that LPS-induced production of macrophage and splenic TNF-${\alpha}$ and Con A-induced production of thymic IFN-${\gamma}$ were attenuated in BAC lupus compared to lupus control, while LPS-stimulated production of macrophage IL-10, Con A-stimulated production of splenic IL-10 and, $PGE_2$-reduced production of splenic IFN-${\gamma}$ enhanced. Therefore, these findings suggest that baicalin may protect from autoimmunity and disease activity in lupus via modulatory effect of proinflammatory cytokine overproduction and Th cytokine imbalance.