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Updated: Apr 4, 2026

Isolation and Characterization of Dendritic Cells and Macrophages from the Mouse Intestine
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A unique CD4⁺ T cell subset expressing granzyme K is regulated by transcription factor EOMES and important for T

Tian Xie1,2,3, Yizhou Du2, Qihan Wang2

  • 1Institute for Immunology and School of Basic Medical Sciences, Tsinghua University, Beijing, China.

Nature Immunology
|April 2, 2026
PubMed

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.

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