Macrophages （Mφ） are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental process of Mφ to trig...Macrophages （Mφ） are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental process of Mφ to trigger transient activation of monocytes, but the underlying regulatory mechanisms are incompletely understood. Here, we showed that the protein expression of transcription factor C/EBPβ was markedly elevated in tumor-associated Mφ both in vitro and human tumors in situ. The expression of C/EBPβ protein correlated with cytokine production in tumor-activated monocytes. Moreover, we found that C/EBPβ expression was regulated at the post-transcriptional level and correlated with sustained reduction of microRNA-155 （miR-155） in tumor-activated monocytes. Bioinformatic analysis revealed that C/EBPβ is a potential target of miR-155 and luciferase assay confirmed that C/EBPβ translation is suppressed by miR-155 through interaction with the 3＇UTR of C/EBPβ mRNA. Further analysis showed that induction of miR-155 suppressed C/EBPβ protein expression as well as cytokine production in tumor-activated monocytes, an effect which could be mimicked by silencing of C/EBPβ. These results indicate that tumor environment causes a sustained reduction of miR-155 in monocytes/Mφ, which in turn regulates the functional activities of monocytes/Mφ by releasing the translational inhibition of transcription factor C/EBPβ.展开更多
B cells secreting IL-10 functionally are recognized as functional regulatory B(B_(reg))cells;however,direct evidence concerning the phenotype,regulation,and functional and clinical relevance of IL-10-secreting B_(reg)...B cells secreting IL-10 functionally are recognized as functional regulatory B(B_(reg))cells;however,direct evidence concerning the phenotype,regulation,and functional and clinical relevance of IL-10-secreting B_(reg)cells in humans is still lacking.Here,we demonstrate that,although IL-10 itself is anti-inflammatory,IL-10+functional B_(reg)cells in patients with systemic lupus erythematosus(SLE)display aggressive inflammatory features;these features shift their functions away from inducing CD8^(+)T cell tolerance and cause them to induce a pathogenic CD4^(+)T cell response.展开更多
文摘Macrophages （Mφ） are prominent components of solid tumors and exhibit distinct phenotypes in different microenvironments. We have recently found that tumors can alter the normal developmental process of Mφ to trigger transient activation of monocytes, but the underlying regulatory mechanisms are incompletely understood. Here, we showed that the protein expression of transcription factor C/EBPβ was markedly elevated in tumor-associated Mφ both in vitro and human tumors in situ. The expression of C/EBPβ protein correlated with cytokine production in tumor-activated monocytes. Moreover, we found that C/EBPβ expression was regulated at the post-transcriptional level and correlated with sustained reduction of microRNA-155 （miR-155） in tumor-activated monocytes. Bioinformatic analysis revealed that C/EBPβ is a potential target of miR-155 and luciferase assay confirmed that C/EBPβ translation is suppressed by miR-155 through interaction with the 3＇UTR of C/EBPβ mRNA. Further analysis showed that induction of miR-155 suppressed C/EBPβ protein expression as well as cytokine production in tumor-activated monocytes, an effect which could be mimicked by silencing of C/EBPβ. These results indicate that tumor environment causes a sustained reduction of miR-155 in monocytes/Mφ, which in turn regulates the functional activities of monocytes/Mφ by releasing the translational inhibition of transcription factor C/EBPβ.
基金The study was supported by project grants from the National Natural Science Foundation of China(82071767,82025016,31830025,81901585,and 81802403)the Natural Science Foundation of Guangdong Province,China(2018B030308010 and 2019A1515011770).
文摘B cells secreting IL-10 functionally are recognized as functional regulatory B(B_(reg))cells;however,direct evidence concerning the phenotype,regulation,and functional and clinical relevance of IL-10-secreting B_(reg)cells in humans is still lacking.Here,we demonstrate that,although IL-10 itself is anti-inflammatory,IL-10+functional B_(reg)cells in patients with systemic lupus erythematosus(SLE)display aggressive inflammatory features;these features shift their functions away from inducing CD8^(+)T cell tolerance and cause them to induce a pathogenic CD4^(+)T cell response.
