iScience (Jul 2025)

AF6 regulates intestinal IgA via crosstalk between intestinal epithelial cells and immune cells in inflammatory bowel disease

  • Liying Lu,
  • Keying Xu,
  • Huiheng Qu,
  • Lele Song,
  • Yanan Song,
  • Yanjun Wu,
  • Xia Sun,
  • Jingwen Kong,
  • Qian Wen,
  • Jiazheng Jiao,
  • Zhanju Liu,
  • Jiazeng Xia,
  • Lixing Zhan

DOI
https://doi.org/10.1016/j.isci.2025.112658
Journal volume & issue
Vol. 28, no. 7
p. 112658

Abstract

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Summary: The pathogenic factors of inflammatory bowel disease (IBD) are very complex, and further investigation of its pathogenesis is necessary. Some polar proteins have been reported to perform functions other than maintaining cell structure. In this study, we reported that the polar protein AF6 expressed by intestinal epithelial cells (IEC) can regulate the expression of MHCII in epithelial cells, thus affecting the cross dialogue between IECs and immune cells, and promoting the secretion of IgA by B cells to play a protective function. IgA supplementation can also improve the severe colitis phenotype caused by AF6 loss. Our study provides an understanding of the regulatory mechanisms of the intestinal epithelial expression of MHC II and its important role in colitis, which will aid in treatment and intervention.

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