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Production of IFN-α by Natural IFN-α Producing Cells (NIPC), induced by apoptotic cells and autoantibodies via FcγRII, could be a pivotal event in the etiopathogenesis of SLE
Arthritis Research & Therapy volume 4, Article number: 7 (2002)
Patients with SLE have an activated type I IFN system, and serum IFN-α levels correlate to both disease activity and severity. We have shown that SLE patients have an IFN-α inducing factor (SLE-IIF) in serum, consisting of anti-DNA antibodies and DNA in complex. The DNA could originate from apoptotic cells that are present in increased numbers in SLE patients. We recently demonstrated that IgG from SLE patients, but not normal individuals, together with apoptotic cells stimulate NIPC to produce IFN-α. In the present study we further characterized the interferogenic cell material and the role of different FcR on NIPC for the IFN-α response.
Apoptosis was induced in U937 cells by treatment with UV light and cell supernatant was collected at different time points. Normal PBMCs, costimulated with IFN-α, were cultured with the apoptotic cell material together with purified IgG from SLE patients or from normal individuals, and produced IFN-α was measured in culture supernatants. In some experiments the SLE-IgG was treated by papain or pepsin to obtain Fab and F(ab')2 fragments, respectively. The effect on the IFN-α response by antibodies to CD16, CD32 (FcγRII), and CD64 as well as aggregated IgG was also investigated.
Apoptotic cells release IFN-α inducing material in a time-dependent fashion and more than 1000 U IFN-α/ml was produced in the PBMC cultures, but only when the apoptotic cell material was combined with intact SLE-IgG. Normal IgG, SLE-IgG Fab or F(ab')2 fragments together with apoptotic cell material where unable to induce IFN-α production. Heat-aggregated IgG and anti-CD32 antibodies inhibited the IFN-α response, whereas antibodies to CD16 and CD64 had no effect on the IFN-α response.
NIPC are induced to IFN-α production via the FcγRII by SLE autoantibodies and apoptotic cell material. This observation may explain the observed ongoing IFN-α production in SLE patients and may be of importance for the understanding of the pathogenesis of SLE.
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Rönnblom, L., Lövgren, T., Bsve, U. et al. Production of IFN-α by Natural IFN-α Producing Cells (NIPC), induced by apoptotic cells and autoantibodies via FcγRII, could be a pivotal event in the etiopathogenesis of SLE. Arthritis Res Ther 4, 7 (2002). https://doi.org/10.1186/ar514
- Apoptotic Cell
- U937 Cell
- Pivotal Event
- PBMC Culture