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Background <p>Inflammatory bowel disease (IBD) is characterized by dysregulated T helper immune responses. Crohn’s disease is predominantly associated with excessive Th1 and Th17 responses, while ulcerative colitis displays a more heterogeneous immune profile. However, the molecular mechanisms underlying Th1 cell differentiation in intestinal inflammation remain incompletely understood. CD30, a member of the tumor necrosis factor receptor superfamily, has been implicated in various inflammatory conditions, yet its role in IBD pathogenesis has not been fully elucidated.</p> Objectives <p>This study aimed to investigate the role of CD30 in experimental colitis and its regulation of Th1 cell differentiation through the NF-κB signaling pathway.</p> Methods <p>Acute colitis was induced in wild-type and CD30-deficient mice using 3% dextran sulfate sodium (DSS) for 7 days. CD30 expression in colonic tissues was assessed by immunohistochemistry, quantitative real-time PCR, and Western blot. Naive CD4 + T cells were isolated and stimulated under Th1-polarizing conditions with or without CD30 knockdown using small interfering RNA. Th1 differentiation was evaluated by flow cytometry with verification using T-bet and IL-17&#xa0;A staining, and related transcription factors and cytokines were measured. The NF-κB signaling pathway was examined in lipopolysaccharide (LPS)-stimulated conditions.</p> Results <p>CD30 expression was significantly upregulated in DSS-induced colitis, correlating with increased Th1 markers including T-bet and IFN-γ. In vitro, CD30 knockdown markedly suppressed Th1 cell differentiation from naive CD4 + T cells, reducing IFN-γ + cell proportions among CD4 + T cells and downregulating T-bet, STAT4, and IL-12Rβ2 expression. Mechanistically, CD30 deficiency inhibited NF-κB pathway activation by reducing p65 phosphorylation and preventing IκBα degradation. In vivo, CD30-/- mice exhibited attenuated colitis severity with reduced disease activity index, improved colon length, decreased histological damage, and diminished Th1 cytokine production compared to wild-type littermates.</p> Conclusions <p>CD30 promotes Th1 cell differentiation and exacerbates experimental colitis through NF-κB-dependent mechanisms. These findings identify CD30 as a potential therapeutic target for IBD treatment.</p>

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CD30 knockout attenuates experimental colitis by reducing inflammatory cytokine production

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月13日

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  • Lili Guo,
  • Zhaocai He,
  • Changqing Yang,
  • Xiaorong Chen,
  • Juan Wang

摘要

Background

Inflammatory bowel disease (IBD) is characterized by dysregulated T helper immune responses. Crohn’s disease is predominantly associated with excessive Th1 and Th17 responses, while ulcerative colitis displays a more heterogeneous immune profile. However, the molecular mechanisms underlying Th1 cell differentiation in intestinal inflammation remain incompletely understood. CD30, a member of the tumor necrosis factor receptor superfamily, has been implicated in various inflammatory conditions, yet its role in IBD pathogenesis has not been fully elucidated.

Objectives

This study aimed to investigate the role of CD30 in experimental colitis and its regulation of Th1 cell differentiation through the NF-κB signaling pathway.

Methods

Acute colitis was induced in wild-type and CD30-deficient mice using 3% dextran sulfate sodium (DSS) for 7 days. CD30 expression in colonic tissues was assessed by immunohistochemistry, quantitative real-time PCR, and Western blot. Naive CD4 + T cells were isolated and stimulated under Th1-polarizing conditions with or without CD30 knockdown using small interfering RNA. Th1 differentiation was evaluated by flow cytometry with verification using T-bet and IL-17 A staining, and related transcription factors and cytokines were measured. The NF-κB signaling pathway was examined in lipopolysaccharide (LPS)-stimulated conditions.

Results

CD30 expression was significantly upregulated in DSS-induced colitis, correlating with increased Th1 markers including T-bet and IFN-γ. In vitro, CD30 knockdown markedly suppressed Th1 cell differentiation from naive CD4 + T cells, reducing IFN-γ + cell proportions among CD4 + T cells and downregulating T-bet, STAT4, and IL-12Rβ2 expression. Mechanistically, CD30 deficiency inhibited NF-κB pathway activation by reducing p65 phosphorylation and preventing IκBα degradation. In vivo, CD30-/- mice exhibited attenuated colitis severity with reduced disease activity index, improved colon length, decreased histological damage, and diminished Th1 cytokine production compared to wild-type littermates.

Conclusions

CD30 promotes Th1 cell differentiation and exacerbates experimental colitis through NF-κB-dependent mechanisms. These findings identify CD30 as a potential therapeutic target for IBD treatment.