Increased expression of TLR2 in CD4+ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications
The innate immune system has been shown to play an important pathologic role in systemic lupus erythematosus (SLE). TLR2, a PRR, recognizes exogenous PAMPs, and endogenous damage‐associated molecular patterns and has been implicated in the initiation and maintenance of the perpetuated inflammatory reactions in autoimmune diseases. Here, we report increased expression of TLR2 in CD4 + and CD8 + T cells, CD19 + B cells, and CD14 + monocytes from SLE patients. Conventional treatment, such as hydroxychloroquine and corticosteroids, showed no effect on TLR2 expression in CD4 + T cells from SLE patients. In vitro stimulation of TLR2 in CD4 + T cells from SLE patients increased CD40L and CD70 expression, as well as secretion of IL‐6, IL‐17A, IL‐17F, and TNF‐α, while Foxp3 transcription decreased. This effect was reversed by TLR2 siRNA. Moreover, TLR2 activation upregulated H3K4 tri‐methylation and H4 acetylation levels while downregulated H3K9 tri‐methylation level in the IL‐17A promoter region. In addition, it also increased H4 acetylation levels and decreased H3K9 tri‐methylation levels in the IL‐17F promoter region. In summary, our findings demonstrate that increased expression of TLR2 contributes to immune reactivity and promotes IL‐17A and IL‐17F expression through histone modifications in SLE..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
European journal of immunology - 45(2015), 9, Seite 2683-2693 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Yu [VerfasserIn] |
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| Links: |
Volltext |
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| doi: |
10.1002/eji.201445219 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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OLC1962967913 |
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| 245 | 1 | 0 | |a Increased expression of TLR2 in CD4+ T cells from SLE patients enhances immune reactivity and promotes IL‐17 expression through histone modifications |
| 264 | 1 | |c 2015 | |
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| 520 | |a The innate immune system has been shown to play an important pathologic role in systemic lupus erythematosus (SLE). TLR2, a PRR, recognizes exogenous PAMPs, and endogenous damage‐associated molecular patterns and has been implicated in the initiation and maintenance of the perpetuated inflammatory reactions in autoimmune diseases. Here, we report increased expression of TLR2 in CD4 + and CD8 + T cells, CD19 + B cells, and CD14 + monocytes from SLE patients. Conventional treatment, such as hydroxychloroquine and corticosteroids, showed no effect on TLR2 expression in CD4 + T cells from SLE patients. In vitro stimulation of TLR2 in CD4 + T cells from SLE patients increased CD40L and CD70 expression, as well as secretion of IL‐6, IL‐17A, IL‐17F, and TNF‐α, while Foxp3 transcription decreased. This effect was reversed by TLR2 siRNA. Moreover, TLR2 activation upregulated H3K4 tri‐methylation and H4 acetylation levels while downregulated H3K9 tri‐methylation level in the IL‐17A promoter region. In addition, it also increased H4 acetylation levels and decreased H3K9 tri‐methylation levels in the IL‐17F promoter region. In summary, our findings demonstrate that increased expression of TLR2 contributes to immune reactivity and promotes IL‐17A and IL‐17F expression through histone modifications in SLE. | ||
| 540 | |a Nutzungsrecht: © 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim | ||
| 540 | |a © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 540 | |a © COPYRIGHT 2015 Wiley Subscription Services, Inc. | ||
| 650 | 4 | |a TLR2 | |
| 650 | 4 | |a Systemic lupus erythematosus | |
| 650 | 4 | |a Histone modification | |
| 650 | 4 | |a IL‐17 | |
| 650 | 4 | |a T cells | |
| 650 | 4 | |a Lupus Erythematosus, Systemic - immunology | |
| 650 | 4 | |a Forkhead Transcription Factors - genetics | |
| 650 | 4 | |a Histones - immunology | |
| 650 | 4 | |a Interleukin-17 - genetics | |
| 650 | 4 | |a CD4-Positive T-Lymphocytes - metabolism | |
| 650 | 4 | |a Antigens, CD70 - immunology | |
| 650 | 4 | |a RNA, Small Interfering - genetics | |
| 650 | 4 | |a Antigens, CD70 - genetics | |
| 650 | 4 | |a CD8-Positive T-Lymphocytes - metabolism | |
| 650 | 4 | |a Epigenesis, Genetic - immunology | |
| 650 | 4 | |a B-Lymphocytes - pathology | |
| 650 | 4 | |a CD4-Positive T-Lymphocytes - immunology | |
| 650 | 4 | |a Histones - metabolism | |
| 650 | 4 | |a B-Lymphocytes - immunology | |
| 650 | 4 | |a CD40 Ligand - immunology | |
| 650 | 4 | |a CD40 Ligand - genetics | |
| 650 | 4 | |a Lupus Erythematosus, Systemic - metabolism | |
| 650 | 4 | |a Toll-Like Receptor 2 - immunology | |
| 650 | 4 | |a CD8-Positive T-Lymphocytes - immunology | |
| 650 | 4 | |a Histones - genetics | |
| 650 | 4 | |a CD8-Positive T-Lymphocytes - pathology | |
| 650 | 4 | |a Lupus Erythematosus, Systemic - pathology | |
| 650 | 4 | |a Toll-Like Receptor 2 - genetics | |
| 650 | 4 | |a Lupus Erythematosus, Systemic - genetics | |
| 650 | 4 | |a Interleukin-17 - immunology | |
| 650 | 4 | |a RNA, Small Interfering - immunology | |
| 650 | 4 | |a CD4-Positive T-Lymphocytes - pathology | |
| 650 | 4 | |a B-Lymphocytes - metabolism | |
| 650 | 4 | |a Toll-Like Receptor 2 - antagonists & inhibitors | |
| 650 | 4 | |a Forkhead Transcription Factors - immunology | |
| 650 | 4 | |a Methylation | |
| 650 | 4 | |a B cells | |
| 650 | 4 | |a Lupus | |
| 650 | 4 | |a Lymphocytes | |
| 650 | 4 | |a Autoimmune diseases | |
| 650 | 4 | |a Genes | |
| 700 | 1 | |a Liao, Jieyue |4 oth | |
| 700 | 1 | |a Zhao, Ming |4 oth | |
| 700 | 1 | |a Wu, Haijing |4 oth | |
| 700 | 1 | |a Yung, Susan |4 oth | |
| 700 | 1 | |a Chan, Tak Mao |4 oth | |
| 700 | 1 | |a Yoshimura, Akihiko |4 oth | |
| 700 | 1 | |a Lu, Qianjin |4 oth | |
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| 856 | 4 | 1 | |u http://dx.doi.org/10.1002/eji.201445219 |3 Volltext |
| 856 | 4 | 2 | |u http://onlinelibrary.wiley.com/doi/10.1002/eji.201445219/abstract |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/26079624 |
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