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Michael E Stern, Katherine S Held, Annie Ratanapinta, Christopher S. Schaumburg, Jerry Y Niederkorn, Stephen C Pflugfelder; Baseline Delayed-Type Hypersensitivity and Desiccating Stress- Induced Dry Eye are Significantly Influenced by Thermoneutral Housing Temperature. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):327.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate how murine thermoneutral housing temperature contributes to baseline delayed-type hypersensitivity (DTH) and desiccating stress (DS)-induced dry eye.
To test the hypothesis that thermoneutral (TN) housing conditions can alleviate immune suppression induced by the commonly used sub-TN 22˚C ±2˚C temperature, we exposed C57BL/6 female mice to TN (29˚C ±2˚C) or sub-TN conditions, using a controlled environmental chamber for up to 2 wks. Peripheral and ocular immune responses were evaluated by DTH reaction and dry eye disease. DTH was induced by Mtb in CFA immunization. Ear inflammation was evaluated 24hrs post ear Mtb challenge. Experimental dry eye was induced after 1 wk of TN or sub-TN housing by exposing mice to DS [SC scopolamine 0.1mg/day, 20% RH, and sustained airflow] for up to 6 days, and clinical and histological dry eye evaluated.
Exposure to TN housing temperature did not alter tear production nor corneal fluorescein staining (CFS), however, the number of goblet cells at 1 wk and conjunctiva CD4+ T cells at 1 and 2 wks were significantly increased (p<0.05, p≤0.01, respectively) compared to sub-TN housed controls. Evaluation of DTH immune responses revealed significant increases in ear thickness and weight (p<0.05) of TN housed mice compared to sub-TN controls. In addition, gene expression of key inflammatory markers such as Th1/17-associated cytokines and chemokines were >4-fold upregulated in challenged ears of TN mice, relative to sub-TN mice. Following additional exposure to DS, TN mice showed significantly higher CFS score (9.19 ±0.67, p=0.01), relative to sub-TN mice (7.13 ±0.41), however, this trend did not correlate to a further increase in conjunctiva CD4+ T cells.
These results indicate that exposure to TN housing temperature significantly enhances peripheral immune responses, yet does not modulate ocular surface health, despite increased CD4+ T cell infiltrates. Furthermore, induction of dry eye disease under TN housing temperature enhances corneal epithelial damage without affecting the number of conjunctiva CD4+ T cells, indicating a possible increased pathogenicity of these T cell infiltrates that contributes to greater clinical disease. Collectively, the data suggests that TN housing may contribute to more severe experimental dry eye disease.
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