Back to Search
Start Over
Autoimmune Th2-mediated dacryoadenitis in MRL/MpJ mice becomes Th1-mediated in IL-4 deficient MRL/MpJ mice.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2007 Dec; Vol. 48 (12), pp. 5624-9. - Publication Year :
- 2007
-
Abstract
- 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.<br />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.<br />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).<br />Conclusions: These results suggest that a Th2 autoimmune process can be converted to a Th1 process in the absence of IL-4.
- Subjects :
- Animals
Autoimmune Diseases pathology
B7-1 Antigen metabolism
B7-2 Antigen metabolism
Dacryocystitis pathology
Female
Immunoenzyme Techniques
Interferon-gamma genetics
Interferon-gamma metabolism
Interleukin-13 genetics
Interleukin-13 metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Inbred MRL lpr
Mice, Knockout
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Autoimmune Diseases immunology
Dacryocystitis immunology
Gene Silencing physiology
Interleukin-4 genetics
Th1 Cells immunology
Th2 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0146-0404
- Volume :
- 48
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 18055812
- Full Text :
- https://doi.org/10.1167/iovs.07-0237