Differential Activity of Type I Interferon Subtypes for Dendritic Cell Differentiation

Abstract

The type I interferon (IFN) family comprises 15 cytokines (in human 13 alpha, 1 beta, 1 omega), which exert several cellular functions through binding to a common receptor. Despite initial activation of the same Jak/Stat signalling pathway, the cellular response may differ depending on type I IFN subtype. We investigated the activity of six type I IFN subtypes -IFN alpha 1, alpha 2, alpha 8, alpha 21, omega and beta- to promote the differentiation of dendritic cells (DC). Transcriptome analyses identified two distinct groups, the IFN alpha/omega-DC and the IFN beta-DC. In addition, the expression level of seven chemokines and several cell surface markers characteristic of DC distinguished IFN alpha-DC and IFN beta-DC. These differences are unlikely to impact the efficacy of T cell functional response since IFN alpha 2-DC and IFN beta-DC were equipotent in inducing the proliferation and the polarization of allogenic naive CD4 T cells into Th1 cells and in stimulating autologous antigen specific CD4 or CD8 T cells. Of the functional parameters analysed, the only one that showed a modest differential was the phagocytic uptake of dead cells which was higher for IFN alpha 2-DC.