Regulatory B cells(Bregs)are a functionally defined B cell subset,and IL-10 is crucial for the suppressive functions of Bregs.However,little is known regarding how IL-10 production is regulated in B cells.To explore t...Regulatory B cells(Bregs)are a functionally defined B cell subset,and IL-10 is crucial for the suppressive functions of Bregs.However,little is known regarding how IL-10 production is regulated in B cells.To explore the mechanisms by which IL-10 is regulated in B cells,we used mRNA microarrays to screen for molecules that are upregulated in IL-10-producing B cells and identified RNA-binding motif protein 47(Rbm47)as a post-transcriptional regulator.Rbm47 was found to promote IL-10 production in B cells.We found that Rbm47 promotes the stability of IL-10 mRNA by binding to AU-rich elements in the 3′untranslated region of Il10 mRNA.In addition,we demonstrated that the overexpression of Rbm47 enabled B cells to facilitate Foxp3+regulator T-cell induction and reduce the severity of DSS-induced ulcerative colitis.Taken together,these results suggest that Rbm47 plays an important role in regulating IL-10 at the post-transcriptional level,thus promoting the regulatory functions of B cells.The findings presented in this study not only increase our understanding of the post-translational regulation of IL-10 in B cells but also identify a novel strategy for the potential application of Bregs.展开更多
The complement C5 anaphylatoxin receptor is a member of the seven transmembrane-spanning G protein-coupled receptor superfamily that signals through Gcxi and Gtz16. C5aR is mostly expressed on neutrophils, macrophages...The complement C5 anaphylatoxin receptor is a member of the seven transmembrane-spanning G protein-coupled receptor superfamily that signals through Gcxi and Gtz16. C5aR is mostly expressed on neutrophils, macrophages and endothelial cells. C5a and C5aR interaction plays an important role in numerous biological effects such as in vivo cytokine storm which results in inflammatory damage. Considering the limitation of collection of human peripheral blood neutrophils and their short half life, the stably transfected cell line for studying the biological effects of C5aR is needed. In this study, we transfected C5aR gene into Molt-4 cell line and examined the function of ectopic C5aR. Our results showed stable expression of the C5aR in Molt-4 cell line and their interaction with human C5a induced ERKI/2 phosphorylation, Ca＋＋ influx. This stable transfected cell line may provide a useful tool for studying signal pathways related to C5a and C5aR interplay and antibody development specific for C5aR. Cellular ＆ Molecular Immunology.展开更多
基金supported by National Basic Research Program 973 Grants(2015CB943301)the Key Program of the Beijing Natural Science Foundation(7141007)the National Nature and Science Funds(31770951,31770956 and 81471529).
文摘Regulatory B cells(Bregs)are a functionally defined B cell subset,and IL-10 is crucial for the suppressive functions of Bregs.However,little is known regarding how IL-10 production is regulated in B cells.To explore the mechanisms by which IL-10 is regulated in B cells,we used mRNA microarrays to screen for molecules that are upregulated in IL-10-producing B cells and identified RNA-binding motif protein 47(Rbm47)as a post-transcriptional regulator.Rbm47 was found to promote IL-10 production in B cells.We found that Rbm47 promotes the stability of IL-10 mRNA by binding to AU-rich elements in the 3′untranslated region of Il10 mRNA.In addition,we demonstrated that the overexpression of Rbm47 enabled B cells to facilitate Foxp3+regulator T-cell induction and reduce the severity of DSS-induced ulcerative colitis.Taken together,these results suggest that Rbm47 plays an important role in regulating IL-10 at the post-transcriptional level,thus promoting the regulatory functions of B cells.The findings presented in this study not only increase our understanding of the post-translational regulation of IL-10 in B cells but also identify a novel strategy for the potential application of Bregs.
基金supported by the grants from the National Key Basic Research Program of China(2007CB512406)the National Natural Science Foundation of China(30571732)National"863"Fund Grant of China(2006AA02A254).
文摘The complement C5 anaphylatoxin receptor is a member of the seven transmembrane-spanning G protein-coupled receptor superfamily that signals through Gcxi and Gtz16. C5aR is mostly expressed on neutrophils, macrophages and endothelial cells. C5a and C5aR interaction plays an important role in numerous biological effects such as in vivo cytokine storm which results in inflammatory damage. Considering the limitation of collection of human peripheral blood neutrophils and their short half life, the stably transfected cell line for studying the biological effects of C5aR is needed. In this study, we transfected C5aR gene into Molt-4 cell line and examined the function of ectopic C5aR. Our results showed stable expression of the C5aR in Molt-4 cell line and their interaction with human C5a induced ERKI/2 phosphorylation, Ca＋＋ influx. This stable transfected cell line may provide a useful tool for studying signal pathways related to C5a and C5aR interplay and antibody development specific for C5aR. Cellular ＆ Molecular Immunology.
