Impacts of GFP-FoxP3+ regulatory T cells on lupus hallmarks differ by genetic background and type of GFP knock-in

• Published in: Autoimmunity (Chur, Switzerland) Switzerland), 2019-08, Vol.52 (5-6), p.199-207
• Main Authors: Chang, Soog-Hee, Kim, Tae-Joo, Kim, Yongbaek, Han, Seung Seok, Lee, Sun-Kyung, Sim, Ji Hyun, Kim, Young-Joo, Lee, Se Jeong, Rhyu, Im Joo, Nam, Ki-Hoan, Mohan, Chandra, Kim, Hang-Rae
• Format: Article
• Language: English
• Subjects: anti-nuclear antibodies; green fluorescence protein; lupus; Regulatory T cells; Sle1 gene locus
• ISSN: 0891-6934; 1607-842X
• DOI: 10.1080/08916934.2019.1657098

FoxP3 reporter mice expressing green fluorescence protein (GFP) have been used as a very convenient tool to investigate the impact of regulatory T (Treg) cells on pathogenesis in autoimmune diseases. Here, we found that GFP-FoxP3 + 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 (Sle1) and KI method: contrasting with B6.Sle1.fGFP-FoxP3 mice, expressing GFP via N-terminal insertion, B6.Sle1.iGFP-FoxP3, expressing GFP via bicistronic internal ribosome entry site-driven promotion, exhibited significantly lower penetrance of serum ANA, comparing to control B6.Sle1 mice. Moreover, B6.Sle1.GFP-FoxP3 + mice reduced the Sle1-induced splenomegaly and B-cell expansion independently of the KI method employed, mainly by reducing the numbers of transitional 1 (T1) B cells and CD21 - CD23 - B cells, including plasmablasts and plasma cells. The absolute numbers of both splenic CD4 + T cells and Treg cells from B6.Sle1.GFP-FoxP3 KI mice were significantly reduced but their proportion was not changed, compared to B6.Sle1 mice. Although the glomerular basement membranes were thickened in both B6.Sle1 and B6.Sle1.iGFP-FoxP3 mice, they were thinner in B6.Sle1.fGFP-FoxP3 mice. The latter mice expressed more nephrophilic autoantibodies and deposited more complement component 3 in glomeruli compared to B6.iGFP-FoxP3 mice. FoxP3 + Treg cells may modulate B-cell tolerance in lupus-prone B6.Sle1 mice, presumably by modulating pathogenic, nephrophilic autoantibody production and nephritis.