Abstract：
:A hallmark of autoimmunity in murine models of lupus is the formation of germinal centers (GCs) in lymphoid tissues where self-reactive B cells expand and differentiate. In the host response to foreign antigens, follicular dendritic cells (FDCs) maintain GCs through the uptake and cycling of complement-opsonized immune complexes. Here, we examined whether FDCs retain self-antigens and the impact of this process in autoantibody secretion in lupus. We found that FDCs took up and retained self-immune complexes composed of ribonucleotide proteins, autoantibody, and complement. This uptake, mediated through CD21, triggered endosomal TLR7 and led to the secretion of interferon (IFN) α via an IRF5-dependent pathway. Blocking of FDC secretion of IFN-α restored B cell tolerance and reduced the amount of GCs and pathogenic autoantibody. Thus, FDCs are a critical source of the IFN-α driving autoimmunity in this lupus model. This pathway is conserved in humans, suggesting that it may be a viable therapeutic target in systemic lupus erythematosus.
journal_name
Immunityjournal_title
Immunityauthors
Das A,Heesters BA,Bialas A,O'Flynn J,Rifkin IR,Ochando J,Mittereder N,Carlesso G,Herbst R,Carroll MCdoi
10.1016/j.immuni.2016.12.014subject
Has Abstractpub_date
2017-01-17 00:00:00pages
106-119issue
1eissn
1074-7613issn
1097-4180pii
S1074-7613(16)30520-9journal_volume
46pub_type
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