An IL15-dependent novel immune cell subset with multiple functionalities affecting the onset and severity of autoimmune disease (171.36)

Abstract

Abstract Interferon-producing killer dendritic cells (IKDC) are a recently discovered innate cell subset that shares morphological and functional characteristics of NK and DC cells. The aim of this study is to investigate the role of IKDCs in terms of initiating autoimmune disease. We found that these cells are expanded in mice with multiple copies of the TLR7 gene and that the number of these cells correlates with disease activity. Expansion of this population is due to their cell intrinsic sensitivity to TLR7 stimulation. IKDCs are dependent of IL15, produce high levels of IFN type I and type II after stimulation with a TLR7 agonist, are capable of MHC class II antigen presentation, and can cross-present antigen to CD8 cells. Adoptive transfer of IKDC to wild type mice causes activation of naïve T cells, expansion of inflammatory monocyte populations and IFN-dependent CD8 activation. IKDC adoptive transfer also induces elevated inflammatory cytokine and IgG levels in the serum. We found that IFN type I and CD40/CD40L interactions are essential for the inflammatory effect of these cells. Taken together these results uncover a potential role for this cell populaiton in the development of autoimmune pathologies.