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Background <p>Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease that belongs to the inflammatory bowel disease (IBD). The complex etiology of UC contributes to heterogeneous clinical outcomes in treatment. In clinical practice, approximately 30% of UC patients do not respond to first-line treatment with anti-TNF-α therapy.</p> Methods <p>In this study, we performed single-cell sequencing of intestinal mucosal tissue before (pre) and after (post) anti-TNF-α therapy in UC patients and analyzed it in relation to therapy response (-R) and non-response (-NR).</p> Results <p>We found that immune cell profiles differed between the pre-R and post-R groups. Specifically, the proportion of type 3 conventional dendritic cells (cDC3s) with distinct transcriptomes was lower in the post-R group than in the pre-R group and was not different between the pre-NR and post-NR groups. Cell trajectory analysis revealed that the number of cells differentiated into cDC3s significantly decreased in the post-R group, and the genes related to the MAPK signaling pathway obviously increased in these cells. Additionally, the interaction analysis of ligands and receptors revealed that the interactions between HLA-DPA1/DPB1 in fibroblasts and TNFSF9 in cDC3s and between CD44 in fibroblasts and TYROBP in cDC3s were significantly weakened in the post-R group compared to the pre-R group.</p> Conclusion <p>We provide a comprehensive resource detailing the dynamic changes in immune cells during TNF-α therapy in UC patients and identify the reduction in the number of functionally distinct cDC3s as a potential biomarker for predicting anti-TNF-α therapy outcomes.</p>

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Single-cell RNA sequencing reveals the adverse role of cDC3s in the response of ulcerative colitis patients to anti-TNF-α therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月30日

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  • Zhangqin Li,
  • Ruijie Ma,
  • Zhongshun Nie,
  • Youxu Ren,
  • Yunxing Li,
  • Yinglei Miao,
  • Jie Jia,
  • Jiarong Miao

摘要

Background

Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease that belongs to the inflammatory bowel disease (IBD). The complex etiology of UC contributes to heterogeneous clinical outcomes in treatment. In clinical practice, approximately 30% of UC patients do not respond to first-line treatment with anti-TNF-α therapy.

Methods

In this study, we performed single-cell sequencing of intestinal mucosal tissue before (pre) and after (post) anti-TNF-α therapy in UC patients and analyzed it in relation to therapy response (-R) and non-response (-NR).

Results

We found that immune cell profiles differed between the pre-R and post-R groups. Specifically, the proportion of type 3 conventional dendritic cells (cDC3s) with distinct transcriptomes was lower in the post-R group than in the pre-R group and was not different between the pre-NR and post-NR groups. Cell trajectory analysis revealed that the number of cells differentiated into cDC3s significantly decreased in the post-R group, and the genes related to the MAPK signaling pathway obviously increased in these cells. Additionally, the interaction analysis of ligands and receptors revealed that the interactions between HLA-DPA1/DPB1 in fibroblasts and TNFSF9 in cDC3s and between CD44 in fibroblasts and TYROBP in cDC3s were significantly weakened in the post-R group compared to the pre-R group.

Conclusion

We provide a comprehensive resource detailing the dynamic changes in immune cells during TNF-α therapy in UC patients and identify the reduction in the number of functionally distinct cDC3s as a potential biomarker for predicting anti-TNF-α therapy outcomes.