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.
引文