Investigative ophthalmology & visual science · 2007
Autoimmune Th2-mediated dacryoadenitis in MRL/MpJ mice becomes Th1-mediated in IL-4 deficient MRL/MpJ mice.
Сравнительное исследованиеСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Jabs Douglas A, Prendergast Robert A, Campbell Adam L, Lee Bella, Akpek Esen Karamursel, Gérard Hervé C, Hudson Alan P, Whittum-Hudson Judith A
Аннотация
PURPOSE: MRL/MpJ mice of substrains MRL/MpJ-fas(+)/fas(+) (MRL/+) and MRL/MpJ-fas(lpr)/fas(lpr) (MRL/lpr) spontaneously develop autoimmune dacryoadenitis and sialadenitis and are a model for the human disorder Sjögren syndrome. The dacryoadenitis in both substrains appears to be Th2 in nature, with little IFN-gamma and substantial IL-4 at the site of lacrimal gland inflammation.
METHODS: MRL/MpJ mice with a defective IL-4 gene-both MRL/+-IL-4(tm)/IL-4(tm) (MRL/+/IL-4(tm)) and MRL/lpr-IL-4(tm)/IL-4(tm) (MRL/lpr-IL-4(tm))-that resulted in a loss of IL-4 production were bred and evaluated for dacryoadenitis.
RESULTS: MRL/+/IL-4(tm) and MRL/lpr/IL-4(tm) mice developed dacryoadenitis of similar onset, appearance, and severity as found in MRL/MpJ mice with an intact IL-4 gene. Immunohistochemistry examination revealed a substantially greater number of inflammatory cells staining for IFN-gamma than for IL-13 in the dacryoadenitis of IL-4-deficient MRL/MpJ mice (MRL/+/IL-4(tm), 66% vs. 0.8%, P = 0.001; MRL/lpr/IL-4(tm), 67% vs. 1.2%, P = 0.002). Real-time PCR demonstrated greater amounts of IFN-gamma than IL-13 mRNA relative transcripts in lacrimal glands of MRL/lpr/IL-4(tm) mice (mean difference, 28.6; P = 0.035). Greater CD86 (B7-2) than CD80 (B7-1) expression was present in MRL/+/IL-4(tm) mice (11% vs. 3%, P = 0.003) and MRL/lpr/IL-4(tm) mice (10% vs. 3%, P = 0.002).
CONCLUSIONS: These results suggest that a Th2 autoimmune process can be converted to a Th1 process in the absence of IL-4.
METHODS: MRL/MpJ mice with a defective IL-4 gene-both MRL/+-IL-4(tm)/IL-4(tm) (MRL/+/IL-4(tm)) and MRL/lpr-IL-4(tm)/IL-4(tm) (MRL/lpr-IL-4(tm))-that resulted in a loss of IL-4 production were bred and evaluated for dacryoadenitis.
RESULTS: MRL/+/IL-4(tm) and MRL/lpr/IL-4(tm) mice developed dacryoadenitis of similar onset, appearance, and severity as found in MRL/MpJ mice with an intact IL-4 gene. Immunohistochemistry examination revealed a substantially greater number of inflammatory cells staining for IFN-gamma than for IL-13 in the dacryoadenitis of IL-4-deficient MRL/MpJ mice (MRL/+/IL-4(tm), 66% vs. 0.8%, P = 0.001; MRL/lpr/IL-4(tm), 67% vs. 1.2%, P = 0.002). Real-time PCR demonstrated greater amounts of IFN-gamma than IL-13 mRNA relative transcripts in lacrimal glands of MRL/lpr/IL-4(tm) mice (mean difference, 28.6; P = 0.035). Greater CD86 (B7-2) than CD80 (B7-1) expression was present in MRL/+/IL-4(tm) mice (11% vs. 3%, P = 0.003) and MRL/lpr/IL-4(tm) mice (10% vs. 3%, P = 0.002).
CONCLUSIONS: These results suggest that a Th2 autoimmune process can be converted to a Th1 process in the absence of IL-4.