Abstract
MicroRNA (miR) 155 has been implicated in the regulation of innate and adaptive immunity as well as autoimmune processes. Importantly, it has been shown to regulate several antiviral responses, but its contribution to the immune response against cytopathic viruses such as vesicular stomatitis virus (VSV) infections is not known. Using transgenic/recombinant VSV expressing ovalbumin, we show that miR-155 is crucially involved in regulating the T helper cell response against this virus. Our experiments indicate that miR-155 in CD4+ T cells controls their activation, proliferation, and cytokine production in vitro and in vivo upon immunization with OVA as well as during VSV viral infection. Using intravital multiphoton microscopy we analyzed the interaction of antigen presenting cells (APCs) and T cells after OVA immunization and found impaired complex formation when using miR-155 deficient CD4+ T cells compared to wildtype CD4+ T cells ex vivo. In contrast, miR-155 was dispensable for the maturation of myeloid APCs and for their T cell stimulatory capacity. Our data provide the first evidence that miR-155 is required for efficient CD4+ T cell activation during anti-viral defense by allowing robust APC-T cell interaction required for activation and cytokine production of virus specific T cells.
Highlights
T cell activation has to be tightly controlled to allow an efficient immune response against infectious diseases and to prevent autoimmunity
MiR-155 has been shown to be critically important during infection with bacteria, and during viral infection requiring the generation of antiviral CD8+ T cells
We show that lack of miR-155 severely impairs efficient interaction of T cells with antigen presenting cells (APCs), inhibiting subsequent activation and cytokine production of virus specific T cells in a T cell intrinsic fashion
Summary
T cell activation has to be tightly controlled to allow an efficient immune response against infectious diseases and to prevent autoimmunity. MicroRNAs (miRs) have been implicated in both processes and are interesting targets to study immune regulation. MiR-155 has been shown to regulate many aspects of the immune system [1,2,3]. It is involved in the regulation of macrophage and dendritic cell biology, including cytokine production by targeting PU-1 and SHIP-1 [4,5,6]. The increased Th2 differentiation potential of miR-155 deficient CD4+ T cells was attributed to an up-regulation of c-Maf, a potent transcription factor of the IL-4
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