IL-17A primes an early progenitor compartment to tune the erythropoietic feedback circuit
Wu, Q. C.; Swaminathan, A.; Winward, A.; Lalonde, L.; Hwang, Y.; Littman, N.; Socolovsky, M.; Klein, A. M.
Show abstract
Feedback control of erythropoiesis exemplifies conflicting goals in tissue homeostasis: maintaining fast reactivity to stress while minimizing proliferative burden on progenitors in the steady state. Here we show that these conflicting goals are tuned through the combinatorial action of cytokines. We find that IL-17A, a pro-inflammatory cytokine, mediates striking synergism with the negative feedback signal erythropoietin (Epo) in vivo, accelerating the erythropoietic response to hypoxia. A model of erythropoietic control shows increased reactivity may occur through two cell circuit designs, with one having far lower constitutive progenitor burden in normoxia. IL-17A acts through this optimal design by sensitizing progenitors to Epo, a model supported by multiple experimental observations. We suggest that IL-17A signals impending hypoxia during infections, tuning erythropoiesis in favor of a faster stress response. Our study highlights IL-17A as a potential erythropoietic therapeutic agent and serves as a model of homeostatic tuning in stem and progenitor cell circuits.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Leukemic stem cells hijack lineage inappropriate signalling pathways to promote their growth 96%
- Expression of terminal deoxynucleotidyl transferase (TdT) identifies lymphoid-primed progenitors in human bone marrow 96%
- Cross-species analysis identifies conserved transcriptional mechanisms of neutrophil maturation 96%
Similar papers in this journal
- Chromatin state barriers enforce an irreversible mammalian cell fate decision 96%
- A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis 96%
- Defective ribosome assembly impairs leukemia stem cell function in a murine model of acute myeloid leukemia 95%
Similar papers in this journal
- Linker Histone H1 subtypes specifically regulate neutrophil differentiation 96%
- Context-Dependent Modification of PFKFB3 in Hematopoietic Stem Cells Promotes Anaerobic Glycolysis and Ensures Stress Hematopoiesis 95%
- Non-canonical H3K79me2-dependent pathways promote the survival of MLL-rearranged leukemia 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.