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Local triggering of the ICOS coreceptor by CD11c(+) myeloid cells drives organ
inflammation in lupus
#MMPMID25786178
Teichmann LL
; Cullen JL
; Kashgarian M
; Dong C
; Craft J
; Shlomchik MJ
Immunity
2015[Mar]; 42
(3
): 552-65
PMID25786178
show ga
The inducible T cell costimulator (ICOS) is a potent promoter of organ
inflammation in murine lupus. ICOS stimulates T follicular helper cell
differentiation in lymphoid tissue, suggesting that it might drive autoimmunity
by enhancing autoantibody production. Yet the pathogenic relevance of this
mechanism remains unclear. It is also unknown whether other ICOS-induced
processes might contribute to lupus pathology. Here we show that selective
ablation of ICOS ligand (ICOSL) in CD11c(+) cells, but not in B cells,
dramatically ameliorates kidney and lung inflammation in lupus-prone MRL.Fas(lpr)
mice. Autoantibody formation was largely unaffected by ICOSL deficiency in
CD11c(+) cells. However, ICOSL display by CD11c(+) cells in inflamed organs had a
nonredundant role in protecting invading T cells from apoptosis by elevating
activity of the PI3K-Akt signaling pathway, thereby facilitating T cell accrual.
These findings reveal a mechanism that locally sustains organ inflammation in
lupus.
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