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

Author(s):Show less -

Fonseca, Raissa ; 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.

• Document type: Journal article
• Source: NATURE IMMUNOLOGY; v. 23, n. 8, p. 24-pg., 2022-07-26.

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)-beta-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-beta-driven residency program. Ectopic expression of Runx3 in CD4(+) T cells incited this TGF-beta-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. Mackay and colleagues show that distinct programs of tissue residency are induced in CD8(+) and CD4(+) T-RM cell subsets, a difference attributable to the activity of the transcription factor Runx3. (AU)

• FAPESP's process: 19/12431-2 - CD8 regulatory T cells: Friend or foe in routes of infection
• Grantee: Nagela Ghabdan Zanluqui
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate