RRC ID 35993
Author Martinet V, Tonon S, Torres D, Azouz A, Nguyen M, Kohler A, Flamand V, Mao CA, Klein WH, Leo O, Goriely S.
Title Type I interferons regulate eomesodermin expression and the development of unconventional memory CD8(+) T cells.
Journal Nat Commun
Abstract CD8(+) T-cell memory phenotype and function are acquired after antigen-driven activation. Memory-like cells may also arise in absence of antigenic exposure in the thymus or in the periphery. Eomesodermin (Eomes) is a key transcription factor for the development of these unconventional memory cells. Herein, we show that type I interferon signalling in CD8(+) T cells directly activates Eomes gene expression. Consistent with this observation, the phenotype, function and age-dependent expansion of 'virtual memory' CD8(+) T cells are strongly affected in absence of type I interferon signalling. In addition, type I interferons induce a sustained expansion of 'virtual memory' CD8(+) T cells in an Eomes-dependent fashion. We further show that the development of 'innate thymic' CD8(+) T cells is dependent on the same pathway. In conclusion, we demonstrate that type I interferon signalling in CD8(+) T cells drives Eomes expression and thereby regulates the function and homeostasis of memory-like CD8(+) T cells.
Volume 6
Pages 7089
Published 2015-5-8
DOI 10.1038/ncomms8089
PII ncomms8089
PMID 25953241
PMC PMC4432629
MeSH Animals Antigens / metabolism CD8-Positive T-Lymphocytes / drug effects CD8-Positive T-Lymphocytes / metabolism* Gene Expression Regulation / drug effects Homeostasis / drug effects Immunity, Innate / drug effects Immunologic Memory / drug effects Immunologic Memory / genetics* Interferon Type I / metabolism* Interferon-Stimulated Gene Factor 3, gamma Subunit / metabolism Interferon-gamma / biosynthesis Mice, Inbred BALB C Mice, Inbred C57BL Poly I-C / pharmacology Receptor, Interferon alpha-beta / deficiency Receptor, Interferon alpha-beta / metabolism Signal Transduction / drug effects T-Box Domain Proteins / genetics* T-Box Domain Proteins / metabolism Thymocytes / drug effects Thymocytes / metabolism
IF 11.878
Times Cited 6
Mice C.Cg-Irf9<tm1Ttg>/TtgRbrc(RBRC00915)