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T cell factor 1 suppresses CD103+ lung tissue-resident memory T cell development

T cell factor 1 (Tcf1) promotes the central memory CD8+ T (TCM) cell differentiation and stemness in lymphoid tissues after systemic infections. It remains unclear whether Tcf1 regulates the CD103high tissue-resident memory CD8+ T (TRM) cell formation in non-lymphoid tissues after mucosal infections...

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Main Authors: Wu, Jingxia (Author) , Madi, Alaa (Author) , Mieg, Alessa (Author) , Hotz-Wagenblatt, Agnes (Author) , Weisshaar, Nina (Author) , Ma, Sicong (Author) , Mohr, Kerstin (Author) , Schlimbach, Tilo (Author) , Hering, Marvin (Author) , Borgers, Helena (Author) , Cui, Guoliang (Author)
Format: Article (Journal)
Language:English
Published: 7 April 2020
In: Cell reports
Year: 2020, Volume: 31, Issue: 1, Pages: 1-15
ISSN:2211-1247
DOI:10.1016/j.celrep.2020.03.048
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2020.03.048
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S2211124720303624
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Author Notes:Jingxia Wu, Alaa Madi, Alessa Mieg, Agnes Hotz-Wagenblatt, Nina Weisshaar, Sicong Ma, Kerstin Mohr, Tilo Schlimbach, Marvin Hering, Helena Borgers, and Guoliang Cui

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520 |a T cell factor 1 (Tcf1) promotes the central memory CD8+ T (TCM) cell differentiation and stemness in lymphoid tissues after systemic infections. It remains unclear whether Tcf1 regulates the CD103high tissue-resident memory CD8+ T (TRM) cell formation in non-lymphoid tissues after mucosal infections. We find that Tcf1 is progressively decreased during lung TRM cell formation. Abrogation of transforming growth factor β (TGF-β) signaling is associated with a loss of CD103+ and reciprocal gain of Tcf1+ cells among TRM precursors in vivo. T-cell-specific ablation of Tcf7 enhances CD103 protein expression in TRM cells and precursors and increases TRM cell numbers after primary and secondary infections. Tcf1 directly binds to the Itgae (encoding CD103) locus and partly inhibits TGF-β-induced CD103 expression. Our study suggests that memory T cell tissue residency and homeostatic proliferation are reciprocally regulated by Tcf1. Tcf1 may play either immunosupportive or immunosuppressive roles in CD8+ T cells, depending on systemic or mucosal infections. 
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