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

LK Mackay; E Wynne-Jones; D Freestone; DG Pellicci; LA Mielke; DM Newman; A Braun; F Masson; A Kallies; GT Belz; FR Carbone

Journal article

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

LK Mackay, E Wynne-Jones, D Freestone, DG Pellicci, LA Mielke, DM Newman, A Braun, F Masson, A Kallies, GT Belz, FR Carbone

Immunity | CELL PRESS | Published : 2015

DOI: 10.1016/j.immuni.2015.11.008

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..

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University of Melbourne Researchers

Laura Mackay Author

David Freestone Author

Daniel Pellicci Author

Dane Newman Author

Grants

Funding Acknowledgements

We thank members of the Carbone and Heath laboratories for helpful discussions. We also thank J.M. Schenkel (University of Minnesota) for advice on Thy1.1 depletion and IL-15 blocking studies and S. Turner (University of Melbourne) for the influenza virus X31-OVA. This work was supported by National Health and Medical Research Council of Australia (L.K.M. and F.R.C.) and Australian Research Council (L.K.M. and F.R.C.).