| First Author | Yang Q | Year | 2014 |
| Journal | Blood | Volume | 124 |
| Issue | 10 | Pages | 1610-21 |
| PubMed ID | 25030064 | Mgi Jnum | J:214626 |
| Mgi Id | MGI:5603490 | Doi | 10.1182/blood-2014-03-559658 |
| Citation | Yang Q, et al. (2014) COX-1-derived thromboxane A2 plays an essential role in early B-cell development via regulation of JAK/STAT5 signaling in mouse. Blood 124(10):1610-21 |
| abstractText | Cyclooxygenases (COXs) and their prostanoid products play important roles in a diverse range of physiological processes, including in the immune system. Here, we provide evidence that COX-1 is an essential regulator in early stages of B-cell development. COX-1-deficient mice displayed systematic reduction in total B cells, which was attributed to the arrest of early B-cell development from pro-B to pre-B stage. We further demonstrated that this defect was mediated through downregulation of the Janus kinase/signal transducer and activator of transcription 5 (JAK/STAT5) signaling and its target genes, including Pax5, in COX-1(-/-) mice. Mechanistic studies revealed that COX-1-derived thromboxane A2 (TxA2) could regulate JAK3/STAT5 signaling through the cyclic adenosine monophosphate-protein kinase A pathway, via binding with its receptor thromboxane A2 receptor (TP). Administration of the TP agonist could rescue the defective B-cell development and JAK/STAT5 signaling activity in COX-1-deficient mice. Moreover, administration of low-dose aspirin caused a significant reduction in total B cells in peripheral blood of healthy human volunteers, coincidentally with reduced TxA2 production and downregulation of JAK/STAT5 signaling. Taken together, our results demonstrate that COX-1-derived TxA2 plays a critical role in the stage transition of early B-cell development through regulation of JAK/STAT5 signaling and indicate a potential immune-suppressive effect of low-dose aspirin in humans. |
