title: Id2-mediated inhibition of E2A represses memory CD8+ T cell differentiation.
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.
authors.affiliation: Division of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia.
authors.forename: Frederick
authors.initials: F
authors.lastname: Masson
authors.forename: Martina
authors.initials: M
authors.lastname: Minnich
authors.forename: Moshe
authors.initials: M
authors.lastname: Olshansky
authors.forename: Ivan
authors.initials: I
authors.lastname: Bilic
authors.forename: Adele M
authors.initials: AM
authors.lastname: Mount
authors.forename: Axel
authors.initials: A
authors.lastname: Kallies
authors.forename: Terence P
authors.initials: TP
authors.lastname: Speed
authors.forename: Meinrad
authors.initials: M
authors.lastname: Busslinger
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Nutt
authors.forename: Gabrielle T
authors.initials: GT
authors.lastname: Belz
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D051538:Hepatocyte Nuclear Factor 1-alpha; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology*; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051822:T Cell Transcription Factor 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000098815:T-bet Transcription Factor
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D051797:Inhibitor of Differentiation Protein 2; D051822:T Cell Transcription Factor 1; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C496488:Hnf1a protein, mouse; C497452:Idb2 protein, mouse; C075668:Tcf3 protein, mouse
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