Academic Journal
IL-17 stimulates erythropoiesis in vivo by amplifying the response of erythroid progenitors to erythropoietin.
| Title: | IL-17 stimulates erythropoiesis in vivo by amplifying the response of erythroid progenitors to erythropoietin. |
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| Authors: | Wu, Qiu C., Swaminathan, Aishwarya, Winward, Ashley, Lalonde, Logan, Hwang, Yung, Littman, Noah, Socolovsky, Merav, Klein, Allon M. |
| Source: | PLoS Biology; 12/11/2025, Vol. 23 Issue 12, p1-31, 31p |
| Subject Terms: | Interleukin-17, Erythropoietin, Erythrocytes, Cytokines, Hypoxemia, Erythropoiesis |
| Abstract: | 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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| Database: | Complementary Index |
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| Header | DbId: edb DbLabel: Complementary Index An: 190181175 RelevancyScore: 1041 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 1040.81286621094 |
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| Items | – Name: Title Label: Title Group: Ti Data: IL-17 stimulates erythropoiesis in vivo by amplifying the response of erythroid progenitors to erythropoietin. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Wu%2C+Qiu+C%2E%22">Wu, Qiu C.</searchLink><br /><searchLink fieldCode="AR" term="%22Swaminathan%2C+Aishwarya%22">Swaminathan, Aishwarya</searchLink><br /><searchLink fieldCode="AR" term="%22Winward%2C+Ashley%22">Winward, Ashley</searchLink><br /><searchLink fieldCode="AR" term="%22Lalonde%2C+Logan%22">Lalonde, Logan</searchLink><br /><searchLink fieldCode="AR" term="%22Hwang%2C+Yung%22">Hwang, Yung</searchLink><br /><searchLink fieldCode="AR" term="%22Littman%2C+Noah%22">Littman, Noah</searchLink><br /><searchLink fieldCode="AR" term="%22Socolovsky%2C+Merav%22">Socolovsky, Merav</searchLink><br /><searchLink fieldCode="AR" term="%22Klein%2C+Allon+M%2E%22">Klein, Allon M.</searchLink> – Name: TitleSource Label: Source Group: Src Data: PLoS Biology; 12/11/2025, Vol. 23 Issue 12, p1-31, 31p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Interleukin-17%22">Interleukin-17</searchLink><br /><searchLink fieldCode="DE" term="%22Erythropoietin%22">Erythropoietin</searchLink><br /><searchLink fieldCode="DE" term="%22Erythrocytes%22">Erythrocytes</searchLink><br /><searchLink fieldCode="DE" term="%22Cytokines%22">Cytokines</searchLink><br /><searchLink fieldCode="DE" term="%22Hypoxemia%22">Hypoxemia</searchLink><br /><searchLink fieldCode="DE" term="%22Erythropoiesis%22">Erythropoiesis</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 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] – Name: Abstract Label: Group: Ab Data: <i>Copyright of PLoS Biology is the property of Public Library of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1371/journal.pbio.3003462 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 31 StartPage: 1 Subjects: – SubjectFull: Interleukin-17 Type: general – SubjectFull: Erythropoietin Type: general – SubjectFull: Erythrocytes Type: general – SubjectFull: Cytokines Type: general – SubjectFull: Hypoxemia Type: general – SubjectFull: Erythropoiesis Type: general Titles: – TitleFull: IL-17 stimulates erythropoiesis in vivo by amplifying the response of erythroid progenitors to erythropoietin. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Wu, Qiu C. – PersonEntity: Name: NameFull: Swaminathan, Aishwarya – PersonEntity: Name: NameFull: Winward, Ashley – PersonEntity: Name: NameFull: Lalonde, Logan – PersonEntity: Name: NameFull: Hwang, Yung – PersonEntity: Name: NameFull: Littman, Noah – PersonEntity: Name: NameFull: Socolovsky, Merav – PersonEntity: Name: NameFull: Klein, Allon M. IsPartOfRelationships: – BibEntity: Dates: – D: 11 M: 12 Text: 12/11/2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 15449173 Numbering: – Type: volume Value: 23 – Type: issue Value: 12 Titles: – TitleFull: PLoS Biology Type: main |
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