Foxd3 suppresses the production of IL-10~+ regulatory B cells by limiting IL-10 expression
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- 英文论文题名：Foxd3 suppresses the production of IL-10~+ regulatory B cells by limiting IL-10 expression
- 论文作者：Zhang Yu ; Wang Zhiding ; Xiao He ; Shen Beifen ; Li Yan ; Wang Tianxiao ; Wang Renxi
- 英文论文作者：Zhang Yu ; Wang Zhiding ; Xiao He ; Shen Beifen ; Li Yan ; Wang Tianxiao ; Wang Renxi ; Laboratory of Immunology ; Institute of Basic Medical Sciences ; College of Pharmacy ; Henan University
- 年：2016
- 作者机构：Laboratory of Immunology,Institute of Basic Medical Sciences;College of Pharmacy,Henan University;
- 英文论文关键词：Foxd3 ; IL-10 ; Regulatory B cells ; lupus-prone mice
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R392
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：2
- 文件大小：1335k
- 原文格式：D
- 会议级别：全国
摘要
Objective:It is still unclear which key transcription factors determine differentiation of IL-10+ regulatory B cells(Bregs),which play an importance role in restraining the excessive inflammatory responses such as autoimmune diseases by secreting IL-10.Thus, we explore which transcription factor is the key to the expression of IL-10, a pivotal cytokine in Bregs. Methods: We used two webs to predict novel potential transcription factors Foxd3 binding sites in IL-10 promoter region. Chip-PCR assay and IL-10 promoter report system were used to analyze the binding capacity of Foxd3. Foxd3 expression was knocked down by Foxd3 shRNAin B cells to verify its affection on IL-10. In addition, Foxd3 expression was analyzed by WB in lupus-prone MRL/lpr mice.Results: We found that IL-10 promoter had many binding sites for Foxd3. Further, Chip-PCR assay demonstrated that Foxd3 directly bound to the predicted binding sites about start codon upstream-600~-700 bp and-1400 bp, and suppressed the activation of IL-10 promoter. Finally, knock down of Foxd3 could effectively promote Breg production by up-regulating IL-10 expression. Conversely, up-regulated Foxd3 expression was negatively associated with IL-10+ Breg cells in lupus-prone MRL/lpr mice. Conclusions: Our data suggest that Foxd3 suppresses the production of IL-10+ Breg cells by directly binding IL-10 promoter. This study may provide a hint for Breg production and its application to the treatment of autoimmune diseases by regulating Foxd3 expression.
Objective:It is still unclear which key transcription factors determine differentiation of IL-10~+ regulatory B cells(Bregs),which play an importance role in restraining the excessive inflammatory responses such as autoimmune diseases by secreting IL-10.Thus, we explore which transcription factor is the key to the expression of IL-10, a pivotal cytokine in Bregs. Methods: We used two webs to predict novel potential transcription factors Foxd3 binding sites in IL-10 promoter region. Chip-PCR assay and IL-10 promoter report system were used to analyze the binding capacity of Foxd3. Foxd3 expression was knocked down by Foxd3 sh RNAin B cells to verify its affection on IL-10. In addition, Foxd3 expression was analyzed by WB in lupus-prone MRL/lpr mice.Results: We found that IL-10 promoter had many binding sites for Foxd3. Further, Chip-PCR assay demonstrated that Foxd3 directly bound to the predicted binding sites about start codon upstream-600~-700 bp and-1400 bp, and suppressed the activation of IL-10 promoter. Finally, knock down of Foxd3 could effectively promote Breg production by up-regulating IL-10 expression. Conversely, up-regulated Foxd3 expression was negatively associated with IL-10~+ Breg cells in lupus-prone MRL/lpr mice. Conclusions: Our data suggest that Foxd3 suppresses the production of IL-10~+ Breg cells by directly binding IL-10 promoter. This study may provide a hint for Breg production and its application to the treatment of autoimmune diseases by regulating Foxd3 expression.
Objective:It is still unclear which key transcription factors determine differentiation of IL-10~+ regulatory B cells(Bregs),which play an importance role in restraining the excessive inflammatory responses such as autoimmune diseases by secreting IL-10.Thus, we explore which transcription factor is the key to the expression of IL-10, a pivotal cytokine in Bregs. Methods: We used two webs to predict novel potential transcription factors Foxd3 binding sites in IL-10 promoter region. Chip-PCR assay and IL-10 promoter report system were used to analyze the binding capacity of Foxd3. Foxd3 expression was knocked down by Foxd3 sh RNAin B cells to verify its affection on IL-10. In addition, Foxd3 expression was analyzed by WB in lupus-prone MRL/lpr mice.Results: We found that IL-10 promoter had many binding sites for Foxd3. Further, Chip-PCR assay demonstrated that Foxd3 directly bound to the predicted binding sites about start codon upstream-600~-700 bp and-1400 bp, and suppressed the activation of IL-10 promoter. Finally, knock down of Foxd3 could effectively promote Breg production by up-regulating IL-10 expression. Conversely, up-regulated Foxd3 expression was negatively associated with IL-10~+ Breg cells in lupus-prone MRL/lpr mice. Conclusions: Our data suggest that Foxd3 suppresses the production of IL-10~+ Breg cells by directly binding IL-10 promoter. This study may provide a hint for Breg production and its application to the treatment of autoimmune diseases by regulating Foxd3 expression.
引文