Overview

• The University of Osaka team reports the findings in the Journal of Experimental Medicine, led by Mitsuru Arase, Mari Murakami, and Kiyoshi Takeda.
• Single-cell multi-omics profiling of patient gut T cells found an accumulation of tissue-resident memory CD4+ T cells with high RUNX2 and BHLHE40 expression, including a TRM-specific RUNX2 variant.
• Overexpressing RUNX2 and BHLHE40 in healthy donor T cells increased interferon-gamma and granzyme B production and promoted tissue-retentive properties.
• Repressing these factors in patient-derived gut T cells reduced inflammatory activity and decreased retention-associated features ex vivo.
• The authors highlight these transcription factors as potential targets for diagnostics or therapies to prevent relapse in Crohn’s disease, with clinical testing yet to begin.