TY  - JOUR
AU  - Boule, MW
AU  - Broughton, C
AU  - Mackay, F
AU  - Akira, S
AU  - Marshak-Rothstein, A
AU  - Rifkin, IR
Y2  - 2020/12/21
Y1  - 2004/06/21
SN  - 0022-1007
UR  - http://hdl.handle.net/11343/257071
AB  - Dendritic cell (DC) activation by nucleic acid-containing immunoglobulin (Ig)G complexes has been implicated in systemic lupus erythematosus (SLE) pathogenesis. However, the mechanisms responsible for activation and subsequent disease induction are not completely understood. Here we show that murine DCs are much more effectively activated by immune complexes that contain IgG bound to chromatin than by immune complexes that contain foreign protein. Activation by these chromatin immune complexes occurs by two distinct pathways. One pathway involves dual engagement of the Fc receptor FcgammaRIII and Toll-like receptor (TLR)9, whereas the other is TLR9 independent. Furthermore, there is a characteristic cytokine profile elicited by the chromatin immune complexes that distinguishes this response from that of conventional TLR ligands, notably the induction of BAFF and the lack of induction of interleukin 12. The data establish a critical role for self-antigen in DC activation and explain how the innate immune system might drive the adaptive immune response in SLE.
LA  - English
PB  - ROCKEFELLER UNIV PRESS
T1  - Toll-like receptor 9-dependent and -independent dendritic cell activation by chromatin-immunoglobulin G complexes
DO  - 10.1084/jem.20031942
IS  - Journal of Experimental Medicine
VL  - 199
IS  - 12
SP  - 1631-1640
L1  - /bitstream/handle/11343/257071/PMC2212813.pdf?sequence=1&isAllowed=y
ER  -