Journal Article

The microRNA miR-155 controls CD8.sup.+ T cell responses by regulating interferon signaling

Stelekati, Erietta, Turner, Martin, Hope, Jennifer L, Mueller, Yvonne M, Doering, Travis A, Wherry, E. John, Norton, Jillian, Katsikis, Peter D, Gracias, Donald T, Boesteanu, Alina C, Fraietta, Joseph A

2013

Overview

We found upregulation of expression of the microRNA miR-155 in primary effector and effector memory [CD8.sup.+] T cells, but low miR-155 expression in naive and central memory cells. Antiviral [CD8.sup.+] T cell responses and viral clearance were impaired in miR-155-deficient mice, and this defect was intrinsic to [CD8.sup.+] T cells, as miR-155-deficient [CD8.sup.+] T cells mounted greatly diminished primary and memory responses. Conversely, miR-155 overexpression augmented antiviral [CD8.sup.+] T cell responses in vivo. Gene-expression profiling showed that miR-155-deficient [CD8.sup.+] T cells had enhanced type I interferon signaling and were more susceptible to interferon's antiproliferative effect. Inhibition of the type I interferon-associated transcription factors STAT1 or IRF7 resulted in enhanced responses of miR-155-deficient [CD8.sup.+] T cells in vivo. We have thus identified a previously unknown role for miR-155 in regulating responsiveness to interferon and [CD8.sup.+] T cell responses to pathogens in vivo.

• Publisher: Nature Publishing Group
• Subject: Genetic aspects / Health aspects / Interferon / MicroRNA / Physiological aspects / T cells