IL-17 disrupts corneal barrier following desiccating stress.
T helper (Th)-17 is a recently identified subtype of Th response that has been implicated in host defense and autoimmunity. We investigated whether there is evidence for a Th-17 response in human and experimental murine dry eye (DE). Gene expression in the human DE conjunctiva showed increased levels of the Th-17 inducers, interleukin (IL)-23, IL-17A, and interferon-gamma (IFN-gamma). In the murine model, we found that desiccating stress increased matrix metalloproteinase-9, Th-17-associated genes (IL-6, IL-23, transforming growth factor-beta1 and -2, IL-23R, IL-17R, IL-17A, retinoid-related orphan receptor-gammat, and CC chemokine attractant ligand-20) and IFN-gamma in cornea and conjunctiva. Furthermore, we found a significantly increased concentration of IL-17 in tears and number of IL-17-producing cells on the ocular surface. Antibody neutralization of IL-17 ameliorated experimental DE-induced corneal epithelial barrier dysfunction and decreased the expression of matrix metalloproteinases 3 and 9. Taken together, these findings suggest that IL-17 has a role in corneal epithelial barrier disruption in DE.
De Paiva
C S
CS
Department of Ophthalmology, Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, Texas, USA. cintiadp@bcm.tmc.edu
Chotikavanich
S
S
Pangelinan
S B
SB
Pitcher
J D
JD
Fang
B
B
Zheng
X
X
Ma
P
P
Farley
W J
WJ
Siemasko
K F
KF
Niederkorn
J Y
JY
Stern
M E
ME
Li
D-Q
DQ
Pflugfelder
S C
SC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D003228:Conjunctiva / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003315:Cornea / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D019573:Epithelium, Corneal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005123:Eye / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology / Q000502:physiology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012601:Scopolamine; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D016207:Cytokines; D020381:Interleukin-17; D012601:Scopolamine; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse