Increased Expression of Kallikrein 13 in the Lacrimal Functional Unit After Desiccating Stress

Abstract

Purpose: : The purpose of our studies was to evaluate the effects of desiccating stress on expression of kallikrein 13 (Klk13) in the lacrimal functional unit, a recently implicated autoantigen in a mouse model of Sjögren’s syndrome.

Results: : Desiccating stress upregulated Klk13 expression in the cornea and conjunctiva, with immunoreactivity being observed in all epithelial cell layers. In the MG and LG, immunoreactivity increased in ductal epithelia. Immunohistochemical findings were confirmed by western blot analysis, which also showed an increase in 20kDa Klk13 monomer and decrease in the 80KDa Klk13/EGF complex in the cornea and conjunctiva. DS significantly increased levels of Klk13 transcripts in cornea and conjunctiva of DS10 mice compared to NS controls. Similar findings were observed in humans, where compared to control a significant 2-fold mean increase in the level of Klk13 mRNA was found in conjunctival epithelia obtained from dry eye patients. Serum isolated from mice subjected to DS for 10 days contained antibodies specific for recombinant human Klk13, while control serum did not cross-react.

Conclusions: : Based on these findings, we contend that DS increases immune exposure of Klk13 protein through increased expression and epitope unmasking in all tissues of the LFU. Taken together these results suggest that Klk13 is a candidate autoantigen for the autoimmune lacrimal keratoconjunctivitis that develops during experimental desiccating stress.

Keywords: cornea: tears/tear film/dry eye • autoimmune disease • lacrimal gland