Spontaneous T cell mediated keratoconjunctivitis in Aire-deficient mice.
OBJECTIVE
Patients with autoimmune polyendocrinopathy-candiasis-ectodermal dystrophy (APECED) develop severe keratoconjunctivitis, corneal scarring and visual loss, but the precise pathogenesis is unknown. This study evaluated the ocular surface immune cell environment, conjunctival goblet cell density and response to desiccating environmental stress of the autoimmune regulatory (Aire) gene knockout murine model of APECED.


METHODS
Aire-deficient and wild type (WT) mice were subjected to desiccating stress from a drafty, low-humidity environment and pharmacological inhibition of tear secretion for 5 days. Immune cell populations (CD4(+), CD8(+), CD11b(+), CD45(+)) and goblet cell density were measured in ocular surface tissues and meibomian glands, and compared with baseline values.


RESULTS
Greater CD4(+) T cell populations were observed in the conjunctival epithelium of Aire-deficient mice (p<0.001) compared with WT. Aire-deficient mice also had greater numbers of CD4(+), CD8(+), and CD11b(+) cells in the peripheral cornea at baseline and following desiccating stress. The meibomian glands of Aire-deficient mice demonstrated greater CD4(+), CD8(+), CD45(+) and CD11b(+) cells at baseline (p<0.001) and following desiccating stress. Conjunctival goblet cell density was lower at baseline and following desiccating stress in Aire-deficient compared with WT mice (p<0.001).


CONCLUSIONS
Aire-deficiency leads to infiltration of CD4(+) and CD8(+) T cells on the ocular surface and meibomian glands, which is accompanied by goblet cell loss. Desiccating stress promotes this proinflammatory milieu. Immune-mediated mechanisms play a role in the severe blepharitis and keratoconjunctivitis in the murine model of APECED.
Yeh
S
S
Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas 77030, USA.
de Paiva
C S
CS
Hwang
C S
CS
Trinca
K
K
Lingappan
A
A
Rafati
J K
JK
Farley
W J
WJ
Li
D-Q
DQ
Pflugfelder
S C
SC
D000818:Animals; D020397:Goblet Cells / Q000276:immunology*; D007637:Keratoconjunctivitis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014157:Transcription Factors / Q000172:deficiency*; D000096927:AIRE Protein
D014157:Transcription Factors; D000096927:AIRE Protein