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<p>CD4<sup>+</sup> T cells are key drivers of immune-mediated tissue damage and participate in complex cellular interactions that perpetuate chronic inflammation. However, the specific subsets of pathogenic CD4<sup>+</sup> T cells and their non-immune cell partners are less well characterized. Here, we use a mouse model of primary Sjögren disease (pSjD) and identify CD153<sup>+</sup>CD4<sup>+</sup> T cells as critical drivers of inflammation during the early stages of autoimmune pathology. We describe a CD153<sup>+</sup>CD4<sup>+</sup> T cell-CD30<sup>+</sup> tissue-resident fibroblast interaction that promotes fibroblast proliferation and chemokine secretion, further driving immune cell infiltration and thereby amplifying the autoimmune response. Importantly, deletion of CD153 in CD4<sup>+</sup> T cells or neutralization of fibroblast-derived chemokines reduces lymphocytic infiltration and significantly halts autoimmune-like pathology. The CD153-CD30 axis positively correlates with disease severity in human patients. Thus, our results describe a pathogenic, therapeutically targetable CD153<sup>+</sup>CD4<sup>+</sup> T cell-CD30<sup>+</sup> fibroblast axis that perpetuates chronic inflammation in pSjD.</p>

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A CD4+ T cell-fibroblast crosstalk exacerbates autoimmunity in a mouse model of primary Sjögren disease

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月12日

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  • Kunihiro Otsuka,
  • Hiroyuki Kondo,
  • Shin-Ichi Tsukumo,
  • Daisuke Kurotaki,
  • Kei-ichiro Yasunaga,
  • Aya Ushio,
  • Ruka Nagao,
  • Keiko Aota,
  • Yoshiaki Kitamura,
  • Takaaki Tsunematsu,
  • Hideo Yagita,
  • Naozumi Ishimaru,
  • Junko Morimoto,
  • Koji Yasutomo

摘要

CD4+ T cells are key drivers of immune-mediated tissue damage and participate in complex cellular interactions that perpetuate chronic inflammation. However, the specific subsets of pathogenic CD4+ T cells and their non-immune cell partners are less well characterized. Here, we use a mouse model of primary Sjögren disease (pSjD) and identify CD153+CD4+ T cells as critical drivers of inflammation during the early stages of autoimmune pathology. We describe a CD153+CD4+ T cell-CD30+ tissue-resident fibroblast interaction that promotes fibroblast proliferation and chemokine secretion, further driving immune cell infiltration and thereby amplifying the autoimmune response. Importantly, deletion of CD153 in CD4+ T cells or neutralization of fibroblast-derived chemokines reduces lymphocytic infiltration and significantly halts autoimmune-like pathology. The CD153-CD30 axis positively correlates with disease severity in human patients. Thus, our results describe a pathogenic, therapeutically targetable CD153+CD4+ T cell-CD30+ fibroblast axis that perpetuates chronic inflammation in pSjD.