Runx3 drives a CD8(+) T cell tissue residency program that is absent in CD4(+) T cells
- Author(s)
- Fonseca, R; Burn, TN; Gandolfo, LC; Devi, S; Park, SL; Obers, A; Evrard, M; Christo, SN; Buquicchio, FA; Lareau, CA; McDonald, KM; Sandford, SK; Zamudio, NM; Zanluqui, NG; Zaid, A; Speed, TP; Satpathy, AT; Mueller, SN; Carbone, FR; Mackay, LK;
- Details
- Publication Year 2022-07-26,Volume 23,Issue #8,Page 1236-1245
- Journal Title
- Nature Immunology
- Abstract
- Tissue-resident memory T cells (T(RM) cells) 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(+) T(RM) cells lacked the transforming growth factor (TGF)-β-responsive transcriptional network that underpins the tissue residency of epithelial CD8(+) T(RM) cells. While CD4(+) T(RM) cell formation required Runx1, this, along with the modest expression of Runx3 in CD4(+) T(RM) cells, 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(+) T(RM) cell subsets that is attributable to divergent Runx3 activity.
- Publisher
- NPG
- Research Division(s)
- Bioinformatics
- PubMed ID
- 35882933
- Publisher's Version
- https://doi.org/10.1038/s41590-022-01273-4
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-08-08 09:15:49
Last Modified: 2022-08-08 09:43:14