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

Autor:	Ji Hyun Sim, Seung Seok Han, Yongbaek Kim, Chandra Mohan, Tae Joo Kim, Hang Rae Kim, Sun Kyung Lee, Soog Hee Chang, Ki Hoan Nam, Young Joo Kim, Se Jeong Lee, Im Joo Rhyu
Rok vydání:	2019
Předmět:	030203 arthritis & rheumatology 0301 basic medicine Complement component 3 Anti-nuclear antibody Immunology Autoantibody FOXP3 chemical and pharmacologic phenomena hemic and immune systems Biology medicine.disease Molecular biology Green fluorescent protein Pathogenesis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Gene knockin medicine Immunology and Allergy Nephritis
Zdroj:	Autoimmunity. 52:199-207
ISSN:	1607-842X 0891-6934
DOI:	10.1080/08916934.2019.1657098
Popis:	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.
Databáze:	OpenAIRE
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