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<p>CD4⁺ helper T (T<sub>H</sub>) cells consist of multiple functional subsets defined by specific effector cytokines and transcription factors. Recently, single-cell transcriptomic analyses have revealed possible existence of additional populations. Here we identify a unique CD4⁺ T cell subset in mouse and human colitis characterized by high levels of granzyme K (<i>Gzmk</i>) expression, designated as T<sub>H</sub>K cells. These cells exhibit unique transcriptional signatures, with minimal expression of classical T<sub>H</sub>-defining factors but rather prominent <i>Eomesodermin</i> (<i>Eomes</i>) expression. Notably, T<sub>H</sub>K cell differentiation is independent of T<sub>H</sub>1, T<sub>H</sub>2 and T<sub>H</sub>17 lineages in colitis. EOMES is both necessary and sufficient for T<sub>H</sub>K cell induction, by directly driving the expression of <i>Gzmk</i> and associated effector molecules. Genetic ablation of <i>Eomes</i> ameliorates intestinal immunopathology in a T cell-induced colitis model. The T<sub>H</sub>K transcriptional program seems to be conserved across species and in diverse disease contexts. Our findings establish T<sub>H</sub>K cells as a distinct T<sub>H</sub> cell subtype, and the EOMES–T<sub>H</sub>K axis may serve as a potential therapeutic target in inflammatory diseases.</p>

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A unique CD4⁺ T cell subset expressing granzyme K is regulated by transcription factor EOMES and important for T cell-mediated intestinal inflammation

  • 期刊论文

  • 发表日期：

    2026年4月2日

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  • Tian Xie,
  • Yizhou Du,
  • Qihan Wang,
  • Hao Zhang,
  • Kun Wei,
  • Xinxin Chi,
  • Xue Bai,
  • Yujie Fu,
  • Zhilin Peng,
  • Yicheng Zhu,
  • Qiuyan Lan,
  • Chen Dong

摘要

CD4⁺ helper T (TH) cells consist of multiple functional subsets defined by specific effector cytokines and transcription factors. Recently, single-cell transcriptomic analyses have revealed possible existence of additional populations. Here we identify a unique CD4⁺ T cell subset in mouse and human colitis characterized by high levels of granzyme K (Gzmk) expression, designated as THK cells. These cells exhibit unique transcriptional signatures, with minimal expression of classical TH-defining factors but rather prominent Eomesodermin (Eomes) expression. Notably, THK cell differentiation is independent of TH1, TH2 and TH17 lineages in colitis. EOMES is both necessary and sufficient for THK cell induction, by directly driving the expression of Gzmk and associated effector molecules. Genetic ablation of Eomes ameliorates intestinal immunopathology in a T cell-induced colitis model. The THK transcriptional program seems to be conserved across species and in diverse disease contexts. Our findings establish THK cells as a distinct TH cell subtype, and the EOMES–THK axis may serve as a potential therapeutic target in inflammatory diseases.