Λεπτομέρειες βιβλιογραφικής εγγραφής
| Τίτλος: |
IL-17 stimulates erythropoiesis in vivo by amplifying the response of erythroid progenitors to erythropoietin. |
| Συγγραφείς: |
Wu, Qiu C., Swaminathan, Aishwarya, Winward, Ashley, Lalonde, Logan, Hwang, Yung, Littman, Noah, Socolovsky, Merav, Klein, Allon M. |
| Πηγή: |
PLoS Biology; 12/11/2025, Vol. 23 Issue 12, p1-31, 31p |
| Θεματικοί όροι: |
Interleukin-17, Erythropoietin, Erythrocytes, Cytokines, Hypoxemia, Erythropoiesis |
| Περίληψη: |
Red blood cell production is regulated by erythropoietin (Epo), maintaining tissue oxygen tension in the steady state and in response to stress. To date, only a handful of factors other than Epo are known to stimulate erythropoiesis, limiting therapeutic options. We recently found that IL-17, a pleiotropic pro-inflammatory cytokine, interacts synergistically with Epo to increase formation of erythroid colonies in vitro. Here, we administered IL-17 to mice to determine whether it accelerates erythropoiesis in vivo. We found that while IL-17 alone had little effect on erythroid and other hematopoietic lineages, combined treatment with both IL-17 and Epo generated a specific and strong synergistic response in erythroid progenitors that significantly increased erythropoietic rate. IL-17 administration also accelerated the erythropoietic response of mice to hypoxia. Single-cell transcriptomic analysis showed that IL-17 acts by sensitizing erythroid progenitors to Epo, rather than through a distinct transcriptional response. Using a dynamical model, we propose that this mechanism optimizes conflicting requirements in the regulation of erythropoiesis, balancing the need for low-cost maintenance of the steady state, with a sufficiently fast stress response. Further, our findings suggest a potentially broadly applicable mechanism whereby pleiotropic cytokines are able to exert lineage-specific effects when their actions are dependent on synergism with lineage-specific factors. Erythropoietin (Epo) can be an effective anemia treatment, but is ineffective or contraindicated in anemia associated with cancer or chronic disease. This study identifies the pleiotropic cytokine IL-17A as a specific stimulator of erythropoiesis in vivo that acts by amplifying the response of erythroid progenitors to Epo. [ABSTRACT FROM AUTHOR] |
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| Βάση Δεδομένων: |
Complementary Index |