| First Author | Das A | Year | 2017 |
| Journal | Immunity | Volume | 46 |
| Issue | 1 | Pages | 106-119 |
| PubMed ID | 28099860 | Mgi Jnum | J:257964 |
| Mgi Id | MGI:6113789 | Doi | 10.1016/j.immuni.2016.12.014 |
| Citation | Das A, et al. (2017) Follicular Dendritic Cell Activation by TLR Ligands Promotes Autoreactive B Cell Responses. Immunity 46(1):106-119 |
| abstractText | 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) alpha via an IRF5-dependent pathway. Blocking of FDC secretion of IFN-alpha restored B cell tolerance and reduced the amount of GCs and pathogenic autoantibody. Thus, FDCs are a critical source of the IFN-alpha 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. |
