The role of a novel IL-12 family cytokine-IL-39 in lupus-prone mice
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- 英文论文题名：The role of a novel IL-12 family cytokine-IL-39 in lupus-prone mice
- 论文作者：Wang Renxi
- 英文论文作者：Wang Renxi ; Beijing Institute of Basic Medical Sciences
- 年：2016
- 作者机构：Beijing Institute of Basic Medical Sciences;
- 英文论文关键词：IL-12 ; IL-39 ; Lupus ; B cells ; 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：R593.24
- 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：1
- 文件大小：230k
- 原文格式：D
- 会议级别：全国
摘要
Object:Interleukin 12 family cytokine is comprised of an α and a β chain and chain-sharing is a key feature of the IL-12 family of cytokines. Based on pairing rule of IL-12 family member an α and β chain, we and other researchers predict that a novel cytokine is composed of IL-23p19 and Ebi3 heterodimer. Methods: We used qPCR, Western blot, and Co-IP assays to prove IL-23p19/Ebi3 heterodimer(IL-39). ELISA, FACS, and co-IP assays were used to detect IL-39 expression in LPS-stimulated B cells and GL7+ activated B cells. By shRNA technology, we identify the function of IL-39 secreted by GL7+ B cells in inducing neutrophil development and mediating inflammatory response in lupus-prone mice. Polyclonal anti-IL-39 antibody were produced by immunizing the animals with purified IL-39, tested by ELISA and used to treat lupus-prone mice.Results: We describe here a new IL-12 member comprised of IL-23p19/Ebi3 heterodimer(IL-39) that is secreted by LPS-stimulated B cells and GL7+ activated B cells of lupus-like mice. GL7+ B cells up-regulated neutrophils by secreting IL-39, whereas IL-39-deficient GL7+B cells lost the capacity to up-regulate neutrophils in lupus-prone mice. Critically, we found that IL-39-induced neutrophils had a positive feedback on IL-39 expression in activated B cells by secreting B-cell activation factor(BAFF). Finally, we found that anti-IL-39 polyclonal antibody reduced inflammatory cells, antibody-secreting B cells, antibody titer in the sera and urine protein in lupus-like mice. Conclusion: These results suggest that IL-39 plays an important role in inflammation in lupus-prone mice and may provide a new therapeutic target for autoimmune diseases like SLE.
Object:Interleukin 12 family cytokine is comprised of an α and a β chain and chain-sharing is a key feature of the IL-12 family of cytokines. Based on pairing rule of IL-12 family member an α and β chain, we and other researchers predict that a novel cytokine is composed of IL-23p19 and Ebi3 heterodimer. Methods: We used q PCR, Western blot, and Co-IP assays to prove IL-23p19/Ebi3 heterodimer(IL-39). ELISA, FACS, and co-IP assays were used to detect IL-39 expression in LPS-stimulated B cells and GL7+ activated B cells. By sh RNA technology, we identify the function of IL-39 secreted by GL7+ B cells in inducing neutrophil development and mediating inflammatory response in lupus-prone mice. Polyclonal anti-IL-39 antibody were produced by immunizing the animals with purified IL-39, tested by ELISA and used to treat lupus-prone mice.Results: We describe here a new IL-12 member comprised of IL-23p19/Ebi3 heterodimer(IL-39) that is secreted by LPS-stimulated B cells and GL7+ activated B cells of lupus-like mice. GL7+ B cells up-regulated neutrophils by secreting IL-39, whereas IL-39-deficient GL7+B cells lost the capacity to up-regulate neutrophils in lupus-prone mice. Critically, we found that IL-39-induced neutrophils had a positive feedback on IL-39 expression in activated B cells by secreting B-cell activation factor(BAFF). Finally, we found that anti-IL-39 polyclonal antibody reduced inflammatory cells, antibody-secreting B cells, antibody titer in the sera and urine protein in lupus-like mice. Conclusion: These results suggest that IL-39 plays an important role in inflammation in lupus-prone mice and may provide a new therapeutic target for autoimmune diseases like SLE.
Object:Interleukin 12 family cytokine is comprised of an α and a β chain and chain-sharing is a key feature of the IL-12 family of cytokines. Based on pairing rule of IL-12 family member an α and β chain, we and other researchers predict that a novel cytokine is composed of IL-23p19 and Ebi3 heterodimer. Methods: We used q PCR, Western blot, and Co-IP assays to prove IL-23p19/Ebi3 heterodimer(IL-39). ELISA, FACS, and co-IP assays were used to detect IL-39 expression in LPS-stimulated B cells and GL7+ activated B cells. By sh RNA technology, we identify the function of IL-39 secreted by GL7+ B cells in inducing neutrophil development and mediating inflammatory response in lupus-prone mice. Polyclonal anti-IL-39 antibody were produced by immunizing the animals with purified IL-39, tested by ELISA and used to treat lupus-prone mice.Results: We describe here a new IL-12 member comprised of IL-23p19/Ebi3 heterodimer(IL-39) that is secreted by LPS-stimulated B cells and GL7+ activated B cells of lupus-like mice. GL7+ B cells up-regulated neutrophils by secreting IL-39, whereas IL-39-deficient GL7+B cells lost the capacity to up-regulate neutrophils in lupus-prone mice. Critically, we found that IL-39-induced neutrophils had a positive feedback on IL-39 expression in activated B cells by secreting B-cell activation factor(BAFF). Finally, we found that anti-IL-39 polyclonal antibody reduced inflammatory cells, antibody-secreting B cells, antibody titer in the sera and urine protein in lupus-like mice. Conclusion: These results suggest that IL-39 plays an important role in inflammation in lupus-prone mice and may provide a new therapeutic target for autoimmune diseases like SLE.
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