Format

Send to

Choose Destination
Immunity. 2015 Dec 15;43(6):1101-11. doi: 10.1016/j.immuni.2015.11.008.

T-box Transcription Factors Combine with the Cytokines TGF-β and IL-15 to Control Tissue-Resident Memory T Cell Fate.

Author information

1
Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia. Electronic address: lkmackay@unimelb.edu.au.
2
Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia.
3
Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Parkville, Victoria 3010, Australia; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia.
4
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
5
Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria 3084, Australia; School of Cancer Medicine, La Trobe University, Melbourne, Victoria 3086, Australia.

Abstract

Tissue-resident memory T (Trm) cells contribute to local immune protection in non-lymphoid tissues such as skin and mucosa, but little is known about their transcriptional regulation. Here we showed that CD8(+)CD103(+) Trm cells, independent of circulating memory T cells, were sufficient for protection against infection and described molecular elements that were crucial for their development in skin and lung. We demonstrated that the T-box transcription factors (TFs) Eomes and T-bet combined to control CD8(+)CD103(+) Trm cell formation, such that their coordinate downregulation was crucial for TGF-β cytokine signaling. TGF-β signaling, in turn, resulted in reciprocal T-box TF downregulation. However, whereas extinguishment of Eomes was necessary for CD8(+)CD103(+) Trm cell development, residual T-bet expression maintained cell surface interleukin-15 (IL-15) receptor β-chain (CD122) expression and thus IL-15 responsiveness. These findings indicate that the T-box TFs control the two cytokines, TGF-β and IL-15, which are pivotal for CD8(+)CD103(+) Trm cell development and survival.

KEYWORDS:

T-box transcription factors; TGF-β; Tissue-resident memory T cells; peripheral immunity

PMID:
26682984
DOI:
10.1016/j.immuni.2015.11.008
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center