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December 8, 2025Blood

Disruption of IL-10 receptor signaling promotes hematopoietic stem cell exhaustion and clonal expansion of JAK2V617F mutant cells during inflammatory stress

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Authors

LWLucas WadleyJHJianhong C HeidmannHLHew Yeng Lai

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Overview

Experimental blockade of IL-10R promotes HSC exhaustion and expansion of JAK2V617F cells, highlighting inflammation's role in myeloid malignancies.

Key Points

  • To investigate the role of IL-10 receptor signaling in hematopoietic stem cell (HSC) regulation during inflammatory conditions.
  • Used TLR4 stimulation with lipopolysaccharide (LPS) to induce inflammation in mice.
  • Examined HSC proliferation, transcriptional changes, and polarity after IL-10 receptor blockade.
  • Conducted competitive transplantation assays to assess HSC function.
  • Analyzed gene expression profiles using RNA-seq.
  • IL-10R blockade prolonged HSC cycling and impaired recovery to quiescence after LPS treatment.
  • Sustained activation of inflammatory pathways was observed in HSCs with IL-10R blockade.
  • Jak2V617F mutant cells demonstrated increased resistance to inflammatory stress and preferential expansion in response to IL-10R disruption.
  • Blockade led to a more aggressive myeloproliferative neoplasm (MPN) phenotype, exhibiting symptoms such as thrombocytosis.

Cite This Study

Wadley et al. (2025) studied this question.

synapsesocial.com/papers/69362f514fa91c937236d976https://doi.org/10.1182/blood-2025-855
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Impaired IL-10 Receptor Signaling Leads to Inflammation Induced Exhaustion in Hematopoietic Stem Cells2025
  2. 2Interleukin-12 and TNFα signaling drives parallel evolution of independent leukemic clones in JAK2V617F mutant myeloproliferative neoplasms2025
  3. 3Maintenance of haematopoietic stem cells by JAK inhibition and increased tyrosine-unphosphorylated STAT52024 · 1 citations
  4. 4Loss of Foxo3a—IL-10 antagonism promotes terminal myelopoiesis via Dgat2-mediated upregulation of lipid droplet accumulation 22539072026
  5. 5HMGA1 chromatin regulators drive transcriptional networks involved in megakaryocyte expansion, fibrosis, and sensitivity to interferon signaling in JAK2-V617F MPN2025