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

Abstract 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.