Here, we found that GFP-FoxP3<sup>+</sup> knock-in (KI) mice showed alterations in the production of anti-nuclear autoantibodies (ANAs) and nephritis with different extent, depending on the presence or absence of lupus susceptibility gene locus 1 (<i>Sle1</i>) and KI method: contrasting with B6.<i>Sle1</i>.fGFP-FoxP3 mice, expressing GFP via N-terminal insertion, B6.<i>Sle1</i>.iGFP-FoxP3, expressing GFP via bicistronic internal ribosome entry site-driven promotion, exhibited significantly lower penetrance of serum ANA, comparing to control B6.<i>Sle1</i> mice.
We followed this by mechanistic work in vitro that resulted in the identification of junctional adhesion molecule A (JAM-A) as a novel important target gene dysregulated by EZH2 in lupus T cells (3).
We followed this by mechanistic work in vitro that resulted in the identification of junctional adhesion molecule A (JAM-A) as a novel important target gene dysregulated by EZH2 in lupus T cells (3).
In the meta-analyses, two CpG sites had a statistically significant non-linear association with MVPA. cg24155427 (p-value=1.19·10), located in an intergenic region in chromosome 1, has been previously associated with smoking, lupus and aging. cg09565397 (p-value=1.59·10), located within DGAT1 in chromosome 8, encodes an enzyme involved in triacylglycerol synthesis and has been associated with body mass index.
Patients with isolated anti-Ro52 had a wider variety of diseases associated, but among auto-immune diseases they were more prone to inflammatory myositis (OR 10.5 [1.4-81.7], <i>p</i> = 0.02) and inflammatory rheumatism (OR 4.6 [1.6-13.8], <i>p</i> = 0.006) in contrast to systemic lupus (OR 0.2 [0.1-0.3], <i>p</i> < 10<sup>-4</sup>) or primary Sjögren's syndrome (OR 0.1 [0.06-0.2], <i>p</i> < 10<sup>-4</sup>).
10-week old female lupus-prone (NZM2328), wild-type (BALB/c) and iNZM mice (lack a functional type I IFN receptor on NZM2328 background) were treated on their dorsal skin with 100 mJ/cm<sup>2</sup> of UVB for 5 consecutive days.
The absence of CD137L causes an immune deviation toward Th17, fewer IL-10-producing CD11b<sup>+</sup> cells and reduced serum IL-10 levels which potentially explain the more severe lupus in DKO mice while leading to reduced microglia activation, lesser cerebral damage and less severe neurological deficits.
Altogether, our results indicate that β2-Glycoprotein I is able to elicit a local Interleukin-17/Interleukin-21 and Interferon-γ inflammation in lupus-antiphospholipid syndrome patients that might lead, if unabated, to plaque instability and subsequent arterial thrombosis, suggesting that the T helper 17/T helper 1 pathway may represent a novel target for the prevention and treatment of the disease.
Here, we show that conventional dendritic cells (cDCs) from predisease lupus-prone B6.NZM Sle1/Sle2/Sle3 triple congenic (TCSle) mice produce more IL-10 than wild-type congenic cDCs upon TLR stimulation, and this overproduction is prevented by blocking the type I IFN receptor (IFNAR) with specific Abs.
A better understanding of the role of IL-10 in B-cell responses and lupus would allow to identify the most promising therapies for individual SLE patients in the future.
Here, we show that conventional dendritic cells (cDCs) from predisease lupus-prone B6.NZM Sle1/Sle2/Sle3 triple congenic (TCSle) mice produce more IL-10 than wild-type congenic cDCs upon TLR stimulation, and this overproduction is prevented by blocking the type I IFN receptor (IFNAR) with specific Abs.
10-week old female lupus-prone (NZM2328), wild-type (BALB/c) and iNZM mice (lack a functional type I IFN receptor on NZM2328 background) were treated on their dorsal skin with 100 mJ/cm<sup>2</sup> of UVB for 5 consecutive days.
Here, we show that conventional dendritic cells (cDCs) from predisease lupus-prone B6.NZM Sle1/Sle2/Sle3 triple congenic (TCSle) mice produce more IL-10 than wild-type congenic cDCs upon TLR stimulation, and this overproduction is prevented by blocking the type I IFN receptor (IFNAR) with specific Abs.
However, the low PKC levels in summer can still decrease further the low production of IL-2 in T cells of lupus patients augmenting the existing AP-1 defects.