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.
Bibliographical noteFunding Information:
This work was supported in part by the Korea Healthcare Technology Research and Development Project, Ministry for Health, Welfare, and Family Affairs (Grant No. HI12C1633 to H.-R. Kim), by the National Research Foundation of Korea funded by the Korean government (Grants Nos. NRF-2019M3A9D5A01102794 and 2017R1A4A1015745 to H.-R. Kim), and by the Seoul National University Hospital Research Fund (Grant No. 0420120530 to H.-R. Kim). The authors thank Dr Alexander Rudensky (Memorial Sloan Kettering Cancer Center) for providing iGFP-FoxP3 KI mice.
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
- Regulatory T cells
- Sle1 gene locus
- anti-nuclear antibodies
- green fluorescence protein
ASJC Scopus subject areas
- Immunology and Allergy