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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Immunol+Res
2018 ; 2018
(ä): 1601079
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Conventional DCs from Male and Female Lupus-Prone B6 NZM Sle1/Sle2/Sle3 Mice
Express an IFN Signature and Have a Higher Immunometabolism That Are Enhanced by
Estrogen
#MMPMID29850618
Lee MH
; Chakhtoura M
; Sriram U
; Caricchio R
; Gallucci S
J Immunol Res
2018[]; 2018
(ä): 1601079
PMID29850618
show ga
Type I interferons (IFN) are pathogenic in systemic lupus erythematosus (SLE) and
were proposed to control the immunometabolism of dendritic cells (DCs). We
previously reported that DCs from female lupus-prone mice constitutively
overexpress IFN-responsive genes resembling the IFN signature found in SLE
patients. As SLE has higher incidence in women than men, more so in women of
reproductive age, estrogens are suggested to affect lupus pathogenesis. We
investigated the effects of sex and estrogens on the IFN signature in
conventional GM-CSF-bone marrow-derived DCs (cDCs), from male and female Triple
Congenic B6.NZM.Sle1/Sle2/Sle3 (TCSle) lupus-prone mice or from wild-type C57BL/6
mice, generated with titrations of 17-beta-estradiol (E2). We found that cDCs
from prediseased TCSle male mice express the IFN signature as female TCSle cDCs
do. Estrogens are necessary but not sufficient to express this IFN signature, but
high doses of E2 can compensate for other steroidal components. E2 stimulation,
regardless of sex, modulates type I IFN-dependent and type I IFN-independent
activation of cDCs in response to TLR stimulation. Finally, we found that TCSle
cDCs from both sexes have elevated markers of immunometabolism and estrogens
enhance the metabolic pathways in cDCs, suggesting a mechanistic link between
estrogens, immunometabolism, and the IFN signature in lupus.