学術雑誌論文

学術雑誌論文

text

The Journal of experimental medicine. 2025, 222(11), p. e20242106

Multi-omics uncovers transcriptional programs of gut-resident memory CD4⁺ T cells in Crohn's disease

Rockefeller University Press

英語

text

2025-09-04

https://doi.org/10.1084/jem.20242106

Arase M., Murakami M., Kihara T., et al. Multi-omics uncovers transcriptional programs of gut-resident memory CD4⁺ T cells in Crohn's disease. The Journal of experimental medicine 222, e20242106 (2025); https://doi.org/10.1084/jem.20242106.

Tissue-resident memory T cells (TRM) remain in nonlymphatic barrier tissues for extended periods and are deeply involved in immune memory at the site of inflammation. Here, we employed multilayered single-cell analytic approaches including chromatin, gene, and protein profiling to characterize a unique CD4⁺ TRM subset present in the inflamed gut mucosa of Crohn's disease patients. We identified two key transcription factors, RUNX2 and BHLHE40, as regulators of pathologically relevant CD4⁺ TRM. These transcriptional regulators work together to induce distinct cellular properties of disease-specific TRM, such as cytotoxicity, T helper 1-effector activity, and tissue retention. Downregulation of RUNX2 and BHLHE40 in patient-derived gut CD4⁺ T cells resulted in the mitigation of the pathogenic phenotype of these cells. Conversely, the ectopic overexpression of both transcription factors in healthy donor-derived CD4⁺ T cells drove IFN-γ pathways and enhanced tissue residency. Our findings illuminate the transcriptional programs driving disease-specific T cell formation in Crohn's disease.

This article is licensed under a Creative Commons Attribution 4.0 International License.

103496

Multi-omics uncovers transcriptional programs of gut-resident memory CD4⁺ T cells in Crohn's disease

Rockefeller University Press

英語

2025-09-04

The Journal of experimental medicine

222

11

e20242106

https://doi.org/10.1084/jem.20242106

https://hdl.handle.net/11094/103496