T Cell Factor 1 Suppresses CD103+ Lung Tissue-Resident Memory T Cell Development

Jingxia Wu; Alaa Madi; Alessa Mieg; Agnes Hotz-Wagenblatt; Nina Weisshaar; Sicong Ma; Kerstin Mohr; Tilo Schlimbach; Marvin Hering; Helena Borgers; Guoliang Cui

doi:10.1016/j.celrep.2020.03.048

T Cell Factor 1 Suppresses CD103+ Lung Tissue-Resident Memory T Cell Development

Cell Rep. 2020 Apr 7;31(1):107484. doi: 10.1016/j.celrep.2020.03.048.

Authors

Affiliations

¹ T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
² T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.
³ Core Facility Omics IT and Data Management, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
⁴ T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany. Electronic address: [email protected].

PMID: 32268106
DOI: 10.1016/j.celrep.2020.03.048

Abstract

T cell factor 1 (Tcf1) promotes the central memory CD8⁺ T (T_CM) cell differentiation and stemness in lymphoid tissues after systemic infections. It remains unclear whether Tcf1 regulates the CD103^high tissue-resident memory CD8⁺ T (T_RM) cell formation in non-lymphoid tissues after mucosal infections. We find that Tcf1 is progressively decreased during lung T_RM 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 T_RM precursors in vivo. T-cell-specific ablation of Tcf7 enhances CD103 protein expression in T_RM cells and precursors and increases T_RM 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.

Keywords: CD103; TRM; Tcf1; influenza; memory CD8+ T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / genetics
Antigens, CD / immunology
Antigens, CD / metabolism*
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / physiology
Cell Differentiation / genetics
Female
Hepatocyte Nuclear Factor 1-alpha / genetics*
Hepatocyte Nuclear Factor 1-alpha / metabolism
Immunologic Memory / genetics
Immunologic Memory / immunology
Integrin alpha Chains / genetics
Integrin alpha Chains / immunology
Integrin alpha Chains / metabolism*
Lung / metabolism
Lymphocyte Activation / immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
T Cell Transcription Factor 1 / genetics
T Cell Transcription Factor 1 / metabolism
Transforming Growth Factor beta / metabolism

Substances

Antigens, CD
Hepatocyte Nuclear Factor 1-alpha
Hnf1a protein, mouse
Integrin alpha Chains
T Cell Transcription Factor 1
Transforming Growth Factor beta
alpha E integrins