Abstract
The transcription factor inhibitor of DNA binding (Id)2 modulates T cell fate decisions, but the molecular mechanism underpinning this regulation is unclear. In this study we show that loss of Id2 cripples effector differentiation and instead programs CD8(+) T cells to adopt a memory fate with increased Eomesodermin and Tcf7 expression. We demonstrate that Id2 restrains CD8(+) T cell memory differentiation by inhibiting E2A-mediated direct activation of Tcf7 and that Id2 expression level mirrors T cell memory recall capacity. As a result of the defective effector differentiation, Id2-deficient CD8(+) T cells fail to induce sufficient Tbx21 expression to generate short-lived effector CD8(+) T cells. Our findings reveal that the Id2/E2A axis orchestrates T cell differentiation through the induction or repression of downstream transcription factors essential for effector and memory T cell differentiation.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors*
-
Basic Helix-Loop-Helix Transcription Factors / genetics
-
Basic Helix-Loop-Helix Transcription Factors / immunology
-
Basic Helix-Loop-Helix Transcription Factors / metabolism*
-
CD8-Positive T-Lymphocytes / cytology
-
CD8-Positive T-Lymphocytes / immunology*
-
CD8-Positive T-Lymphocytes / metabolism
-
Cell Differentiation / genetics
-
Cell Differentiation / immunology*
-
Gene Expression / immunology
-
Hepatocyte Nuclear Factor 1-alpha
-
Immunologic Memory / genetics
-
Immunologic Memory / immunology*
-
Inhibitor of Differentiation Protein 2 / genetics
-
Inhibitor of Differentiation Protein 2 / immunology
-
Inhibitor of Differentiation Protein 2 / metabolism*
-
Mice
-
Mice, Inbred C57BL
-
T Cell Transcription Factor 1 / genetics
-
T Cell Transcription Factor 1 / immunology
-
T Cell Transcription Factor 1 / metabolism
-
T-Box Domain Proteins / genetics
-
T-Box Domain Proteins / immunology
-
T-Box Domain Proteins / metabolism
Substances
-
Basic Helix-Loop-Helix Transcription Factors
-
Hepatocyte Nuclear Factor 1-alpha
-
Hnf1a protein, mouse
-
Idb2 protein, mouse
-
Inhibitor of Differentiation Protein 2
-
T Cell Transcription Factor 1
-
T-Box Domain Proteins
-
T-box transcription factor TBX21
-
Tcf3 protein, mouse