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 previously reported that ex vivo TGF-β and IL-2-induced CD8+CD103+ regulatory T cells (CD8+CD103+ iTregs) displayed similar immunosuppressive effect and therapeutic function on lupus mice nephritis to that of CD4+Foxp3+ Tregs.
Our results suggest that the hCDR1-induced FOXP3 expressing regulatory T cells in lupus are not driven by IDO but rather by other hCDR1 regulated pathways.
Further investigation revealed that treatment with TGP increased the expression of Foxp3 in lupus CD4(+) T cells by down-regulating Foxp3 promoter methylation levels.
We found that the expression level of FOXP3 was significantly higher in urine from patients with active LN than from subjects with inactive lupus and healthy controls (24.5 +/- 45.8 vs 0.8 +/- 1.0 vs 0.6 +/- 0.8 copy; P < 0.001).
The Foxp3 reactivity was less than 10% for cases of dermatomyositis and lupus erythematosus, 23% for hypersensitivity cases, 0% for graft-vs.-host disease, 16% for the dyscrasias and 11% for the lymphomas.