| First Author | Durai V | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 5 | Pages | 1417-1435 |
| PubMed ID | 29572360 | Mgi Jnum | J:261590 |
| Mgi Id | MGI:6155950 | Doi | 10.1084/jem.20171784 |
| Citation | Durai V, et al. (2018) Altered compensatory cytokine signaling underlies the discrepancy between Flt3(-/-) and Flt3l(-/-) mice. J Exp Med 215(5):1417-1435 |
| abstractText | The receptor Flt3 and its ligand Flt3L are both critical for dendritic cell (DC) development, but DC deficiency is more severe in Flt3l(-/-) mice than in Flt3(-/-) mice. This has led to speculation that Flt3L binds to another receptor that also supports DC development. However, we found that Flt3L administration does not generate DCs in Flt3(-/-) mice, arguing against a second receptor. Instead, Flt3(-/-) DC progenitors matured in response to macrophage colony-stimulating factor (M-CSF) or stem cell factor, and deletion of Csf1r in Flt3(-/-) mice further reduced DC development, indicating that these cytokines could compensate for Flt3. Surprisingly, Flt3(-/-) DC progenitors displayed enhanced M-CSF signaling, suggesting that loss of Flt3 increased responsiveness to other cytokines. In agreement, deletion of Flt3 in Flt3l(-/-) mice paradoxically rescued their severe DC deficiency. Thus, multiple cytokines can support DC development, and the discrepancy between Flt3(-/-) and Flt3l(-/-) mice results from the increased sensitivity of Flt3(-/-) progenitors to these cytokines. |
