Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus

Abstract

Genetic impairment of plasmacytoid dendritic cells ameliorates autoantibody production and symptoms of SLE in mice.

Oxidized mitochondrial nucleoids released by neutrophils drive type I interferon production in human lupus

“…Endosomal TLRs play a fundamental role in the IFN production and downstream immune alterations that characterize SLE (Guiducci et al, 2010;Rowland et al, 2014;Sisirak et al, 2014). The origin and nature of the NA ligands that trigger TLR sensors in this disease remain unclear.…”

Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation

“…As pDCs have shown to control certain immune responses through the production of IFN-I, [7][8][9][10][11][12][13][14] we assessed the contribution of the IFN-I signaling to the control of the development of acute DSS-induced colitis using Ifnar1 À / À mice, which lacking IFN-a/b receptor I (IFNAR1). 34 Unexpectively, there was no substantial difference in the BW loss between WT and Ifnar1 À / À mice following oral DSS administration (Supplementary Figure S2a).…”

“…[7][8][9] Furthermore, recent studies have suggested that the activation of pDCs by recognition of self-NA causes elevated IFN-I levels, 10 and this process contributes to the induction of pathogenesis in psoriasis 11 and systemic lupus erythematosus (SLE). [12][13][14] The intestine is the largest compartment of the immune system that is lined by a single layer of epithelium harboring commensal bacteria. 15,16 The gut microbiota contains 10 14 microorganisms, including at least 10 3 different species.…”

Selective HDAC6 inhibition decreases early stage of lupus nephritis by down-regulating both innate and adaptive immune responses

“…To study the mechanism by which selective HDAC6 inhibition prevents the initiation of LN, we focused on the possible changes of the innate immune responses, particularly pDCs, as they have been reported to play a key role in the initiation LN through the production of IFN-a [7,8] Fig. 2a,b).…”

“…In early disease, several studies have shown a critical role for the proinflammatory cytokine interferon (IFN)-a [3][4][5][6]. Additionally, studies using lupus-prone mice have demonstrated that the ablation of plasmacytoid dendritic cells (pDCs), which are the major source of IFNa, prevented lupus nephritis (LN) progression, reduced activation of autoreactive T and B cells and decreased autoantibodies in the circulation and renal deposition [7,8]. These studies highlight the critical involvement of innate immune activation in the initiation of SLE.…”