| First Author | Zhang Y | Year | 2017 |
| Journal | Immunology | Volume | 150 |
| Issue | 4 | Pages | 478-488 |
| PubMed ID | 27995618 | Mgi Jnum | J:246263 |
| Mgi Id | MGI:5923915 | Doi | 10.1111/imm.12701 |
| Citation | Zhang Y, et al. (2017) Foxd3 suppresses interleukin-10 expression in B cells. Immunology 150(4):478-488 |
| abstractText | Interleukin-10-positive (IL-10+ ) regulatory B (Breg) cells play an important role in restraining excessive inflammatory responses by secreting IL-10. However, it is still unclear what key transcription factors determine Breg cell differentiation. Hence, we explore what transcription factor plays a key role in the expression of IL-10, a pivotal cytokine in Breg cells. We used two types of web-based prediction software to predict transcription factors binding the IL-10 promoter and found that IL-10 promoter had many binding sites for Foxd3. Chromatin immunoprecipitation PCR assay demonstrated that Foxd3 directly binds the predicted binding sites around the start codon upstream by -1400 bp. Further, we found that Foxd3 suppressed the activation of IL-10 promoter by using an IL-10 promoter report system. Finally, knocking out Foxd3 effectively promotes Breg cell 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. Hence, our data suggest that Foxd3 suppresses the production of IL-10+ Breg cells by directly binding the IL-10 promoter. This study demonstrates the mechanism for Breg cell production and its application to the treatment of autoimmune diseases by regulating Foxd3 expression. |
