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<p>Interleukin-23 receptor (IL-23R) is a cell surface cytokine receptor classically expressed on T cells, where it regulates T cell activation. Here, we discovered a novel intracellular localization and function for IL-23R in Acute Myeloid Leukemia (AML). Compared to normal hematopoietic cells, IL-23R was increased in primary AML samples. IL-23R was predominantly localized intracellularly in AML cells. BioID mass spectrometry identified mitotic spindle proteins as top interactors with IL-23R. We confirmed interaction between endogenous IL-23R and the mitotic spindle in AML cells and primary AML samples, and this interaction was mediated by IL-23R’s (S/T)x(I/L)P motif. Genetic depletion of IL-23R disrupted mitotic spindle formation and reduced proliferation and stem cell/progenitor function of AML cell lines and primary AML samples. In contrast, depletion of IL-23R spared normal hematopoietic cells and progenitors. Thus, we discovered a novel intracellular function for IL-23R where this receptor regulates mitotic spindle formation and the growth of AML cells.</p>

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Intracellular IL-23R is necessary for mitotic spindle formation and viability in AML

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月17日

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  • Nathan Duong,
  • Dilshad H. Khan,
  • Geethu E. Thomas,
  • Yue Feng,
  • Rose Hurren,
  • Jong Bok Lee,
  • Jonathan St-Germain,
  • Lily Drimmer,
  • Yongran Yan,
  • Lan Xin Zhang,
  • Karen Kai-Lin Fang,
  • Dakai Ling,
  • Mary L. Ma,
  • Neil MacLean,
  • Marcela Gronda,
  • Vincent Rondeau,
  • Brandon D. Brown,
  • Laura Matellán,
  • Courtney L. Jones,
  • Hong Chang,
  • Andrea Arruda,
  • Stephanie Xie,
  • Laurence Pelletier,
  • Mark D. Minden,
  • Li Zhang,
  • Steven M. Kornblau,
  • Brian Raught,
  • Kevin Jacobs,
  • Max G. Jacobs,
  • Daniel Goede,
  • Vito Spadavecchio,
  • Aaron D. Schimmer

摘要

Interleukin-23 receptor (IL-23R) is a cell surface cytokine receptor classically expressed on T cells, where it regulates T cell activation. Here, we discovered a novel intracellular localization and function for IL-23R in Acute Myeloid Leukemia (AML). Compared to normal hematopoietic cells, IL-23R was increased in primary AML samples. IL-23R was predominantly localized intracellularly in AML cells. BioID mass spectrometry identified mitotic spindle proteins as top interactors with IL-23R. We confirmed interaction between endogenous IL-23R and the mitotic spindle in AML cells and primary AML samples, and this interaction was mediated by IL-23R’s (S/T)x(I/L)P motif. Genetic depletion of IL-23R disrupted mitotic spindle formation and reduced proliferation and stem cell/progenitor function of AML cell lines and primary AML samples. In contrast, depletion of IL-23R spared normal hematopoietic cells and progenitors. Thus, we discovered a novel intracellular function for IL-23R where this receptor regulates mitotic spindle formation and the growth of AML cells.