T-box transcription factors combine with the cytokines TGF-beta and IL-15 to control tissue-resident memory T cell fate

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

Author(s): Mackay, LK; Wynne-Jones, E; Freestone, D; Pellicci, DG; Mielke, LA; Newman, DM; Braun, A; Masson, F; Kallies, A; Belz, GT; Carbone, FR;
Details: Publication Year 2015-12-15,Volume 43,Issue #6,Page 1101-11
Journal Title: Immunity
Publication Type: Journal Article
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-beta cytokine signaling. TGF-beta 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 beta-chain (CD122) expression and thus IL-15 responsiveness. These findings indicate that the T-box TFs control the two cytokines, TGF-beta and IL-15, which are pivotal for CD8(+)CD103(+) Trm cell development and survival.
Publisher: Cell Press
Research Division(s): Molecular Immunology
PubMed ID: 26682984
Publisher's Version: https://doi.org/10.1016/j.immuni.2015.11.008
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2016-01-13 02:34:10

Last Modified: 2016-01-13 03:16:05