IL-13 and TGF-β cooperate to promote myelofibrosis. (A) Mast cells, T cells, and potentially other cellular sources of IL-13 are expanded in the bone marrow of prefibrotic mice These cells release profibrotic IL-13, which stimulates the production of transforming growth factor-β (TGF-β) in megakaryocytes. MSC: mesenchymal stem cell. (B) In Jak2V617F mutant megakaryocytes carrying IL-13/IL-4 receptors, IL-13 leads to increased STAT6 phosphorylation (pSTAT6) signaling and increased TGF-β secretion. IL-4Ra: IL-4 receptor alpha. IL13Ra1: IL-13 receptor alpha 1. (C) MPLW515L mutant mice show increased levels of latency-associated peptide (LAP) and glycoprotein-A repetitions predominant protein (GARP), which binds latent TGF-β (LTGF-β) on the cell surface of megakaryocytes. Figure created with BioRender.com.

IL-13 and TGF-β cooperate to promote myelofibrosis. (A) Mast cells, T cells, and potentially other cellular sources of IL-13 are expanded in the bone marrow of prefibrotic mice These cells release profibrotic IL-13, which stimulates the production of transforming growth factor-β (TGF-β) in megakaryocytes. MSC: mesenchymal stem cell. (B) In Jak2V617F mutant megakaryocytes carrying IL-13/IL-4 receptors, IL-13 leads to increased STAT6 phosphorylation (pSTAT6) signaling and increased TGF-β secretion. IL-4Ra: IL-4 receptor alpha. IL13Ra1: IL-13 receptor alpha 1. (C) MPLW515L mutant mice show increased levels of latency-associated peptide (LAP) and glycoprotein-A repetitions predominant protein (GARP), which binds latent TGF-β (LTGF-β) on the cell surface of megakaryocytes. Figure created with BioRender.com.

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