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<p>Context-dependent cytokine granulocyte–macrophage colony-stimulating factor (GM-CSF) plays a crucial role in maintaining intestinal immune homeostasis and exacerbating inflammation. Although multiple cell types produce GM-CSF in the gut, whether intraepithelial lymphocytes (IELs) contribute to GM-CSF production during the steady state remains unclear. In the small intestinal epithelial layer, we identified B220-expressing CD8αα<sup>+</sup> T cells that selectively produced GM-CSF but not interleukin-17A or interferon-γ. Transcriptional analysis combined with weighted parametric gene set analysis revealed the upregulation of retinoid X receptor (RXR)-related genes in this population. Consistently, the RXR agonist bexarotene increased GM-CSF-producing B220<sup>+</sup>CD8αα<sup>+</sup> T cells without affecting other cytokines or CD8αβ<sup>+</sup> T cells. These findings identify B220<sup>+</sup>CD8αα<sup>+</sup> IELs as a spatially distinct source of GM-CSF in the epithelial layer and indicate that the RXR pathway specifically promotes the GM-CSF-producing program, potentially contributing to maintaining immune homeostasis in the small intestine.</p>

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RXR agonist increases newly characterized GM-CSF-producing B220+CD8αα intraepithelial T cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月2日

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  • Yutaka Nakamura,
  • Shintaro Sato

摘要

Context-dependent cytokine granulocyte–macrophage colony-stimulating factor (GM-CSF) plays a crucial role in maintaining intestinal immune homeostasis and exacerbating inflammation. Although multiple cell types produce GM-CSF in the gut, whether intraepithelial lymphocytes (IELs) contribute to GM-CSF production during the steady state remains unclear. In the small intestinal epithelial layer, we identified B220-expressing CD8αα+ T cells that selectively produced GM-CSF but not interleukin-17A or interferon-γ. Transcriptional analysis combined with weighted parametric gene set analysis revealed the upregulation of retinoid X receptor (RXR)-related genes in this population. Consistently, the RXR agonist bexarotene increased GM-CSF-producing B220+CD8αα+ T cells without affecting other cytokines or CD8αβ+ T cells. These findings identify B220+CD8αα+ IELs as a spatially distinct source of GM-CSF in the epithelial layer and indicate that the RXR pathway specifically promotes the GM-CSF-producing program, potentially contributing to maintaining immune homeostasis in the small intestine.