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

Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus. post thumbnail image
Systemic lupus erythematosus (SLE) is an autoimmune dysfunction characterised by the manufacturing of antibodies to self-nucleic acids, immune complicated deposition, and tissue irritation reminiscent of glomerulonephritis. Innate recognition of self-DNA and -RNA and the following manufacturing of cytokines reminiscent of kind I interferons (IFNs) contribute to SLE growth.
Plasmacytoid dendritic cells (pDCs) have been proposed as a supply of pathogenic IFN in SLE; nonetheless, their web contribution to the illness stays unclear. We addressed this query by lowering gene dosage of the pDC-specific transcription issue E2-2 (Tcf4), which causes a selected impairment of pDC operate in in any other case regular animals.
We report that international or DC-specific Tcf4 haplodeficiency ameliorated SLE-like illness brought on by the overexpression of the endosomal RNA sensor Tlr7. Moreover, Tcf4 haplodeficiency within the B6.Sle1.Sle3 multigenic mannequin of SLE practically abolished key illness manifestations together with anti-DNA antibody manufacturing and glomerulonephritis.
Tcf4-haplodeficient SLE-prone animals confirmed a discount of the spontaneous germinal heart response and its related gene expression signature. These outcomes present genetic proof that pDCs are critically concerned in SLE pathogenesis and autoantibody manufacturing, confirming their potential utility as therapeutic targets within the illness.

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