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Cuiyan Tan, Wambui Wandu, Samuel Hinshaw, Chi-Chao Chan, Igal Gery; Th9-induced conjunctival inflammation: A new animal model for allergic conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5871.
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© ARVO (1962-2015); The Authors (2016-present)
Allergic conjunctivitis (AC) is a major ocular disease. The pathogenic cellular mechanisms of AC have been mostly investigated by experimental animal systems in which conjunctival inflammation was induced by exposure of specific allergens at the conjunctiva to lymphocytes pre-sensitized against these allergens. Interleukin (IL)-9 and lymphocytes that specifically expressing this cytokine, Th9 cells, play major roles in allergic reactions and this study records our finding that Th9 cells induce conjunctivitis, a new model for this eye disease.<br />
Naïve CD4 cells transgenically expressing T-cell receptor specific to hen egg lysozyme (HEL) were activated/polarized toward Th1, Th9, or Th17 phenotypes and adoptively transferred (5 million/mouse) into syngeneic recipient mice that transgenically express HEL in their lens. On day 4 and day 7 post cell transfer, recipients’ eyes were collected for histological analysis and RNA samples from the recipients’ conjunctiva were analyzed by nCounter gene expression analysis (NanostringTechnologies) for immunology-related 561 genes.<br />
Severe intraocular inflammatory changes developed in recipients of Th1 and Th17 cells, whereas only mild changes were seen inside eyes of the Th9 recipients. In contrast, minimal or no histological changes were detected in the conjunctival tissues of Th1 and Th17 recipient eyes, while intense conjunctival inflammation was found in the Th9 recipient mice. The allergic type of the inflammatory changes in the Th9 recipient conjunctivas is indicated by the high proportions of eosinophil leukocytes (15-20%). In addition, the gene expression analysis showed that the affected inflammatory gene expression profiles of conjunctival tissue from Th9 recipient were different from those in recipients of Th1 or Th17 cells.<br />
This observation provides a new animal model for allergic conjunctivitis. Our data suggest that IL-9 and Th9 cells are likely to play a role in at least a portion of allergic conjunctivitis cases.
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