Runx3 drives a CD8+T cell tissue residency program that is absent in CD4+T cells

Autor: Fonseca, Raíssa, Burn, Thomas N., Gandolfo, Luke C., Devi, Sapna, Park, Simone L., Obers, Andreas, Evrard, Maximilien, Christo, Susan N., Buquicchio, Frank A., Lareau, Caleb A., McDonald, Keely M., Sandford, Sarah K., Zamudio, Natasha M., Zanluqui, Nagela G., Zaid, Ali, Speed, Terence P., Satpathy, Ansuman T., Mueller, Scott N., Carbone, Francis R., Mackay, Laura K.
Zdroj: Nature Immunology; 20220101, Issue: Preprints p1-10, 10p
Abstrakt: Tissue-resident memory T cells (TRMcells) provide rapid and superior control of localized infections. While the transcription factor Runx3 is a critical regulator of CD8+T cell tissue residency, its expression is repressed in CD4+T cells. Here, we show that, as a direct consequence of this Runx3-deficiency, CD4+TRMcells lacked the transforming growth factor (TGF)-β-responsive transcriptional network that underpins the tissue residency of epithelial CD8+TRMcells. While CD4+TRMcell formation required Runx1, this, along with the modest expression of Runx3 in CD4+TRMcells, was insufficient to engage the TGF-β-driven residency program. Ectopic expression of Runx3 in CD4+T cells incited this TGF-β-transcriptional network to promote prolonged survival, decreased tissue egress, a microanatomical redistribution towards epithelial layers and enhanced effector functionality. Thus, our results reveal distinct programming of tissue residency in CD8+and CD4+TRMcell subsets that is attributable to divergent Runx3 activity.
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