Longitudinal analysis of tear cathepsin S activity levels in male non-obese diabetic mice suggests its potential as an early stage biomarker of Sjögren’s Syndrome

Abstract

Tear CTSS activity is elevated with other early disease indicators, suggesting potential as an early stage biomarker for SS.

Inhibition of Cathepsin S Reduces Lacrimal Gland Inflammation and Increases Tear Flow in a Mouse Model of Sjögren’s Syndrome

“…6A ) . The percentage of LG lymphocytic infiltration of 20-week old mice in this topical study was comparable to that reported in other previous studies using mice of the same age 43–45 . However, gene expression data revealed a 70% reduction of H2-Ab1 gene expression in LG from topical Z-FL-treated mice compared to vehicle (Fig.…”

“…In this study, the effects of systemic and topical CTSS inhibition on features of autoimmune dacryoadenitis in mice with established disease were investigated in two separate cohorts. These cohorts and the relative effectiveness of the Z-FL treatment are not directly comparable for several reasons: the ages of the mice at study termination were different (16- versus 20-weeks); the extent of LG lymphocytic infiltration can be highly variable in NOD mice 43–45 and as shown herein by comparing vehicle-treated mice in Figs 2A and 6A for each cohort; and Z-FL bioavailability with each administration modality was not determined nor optimised. The hypothesis underlying this study is that CTSS inhibition would elicit potential therapeutic benefit in autoimmune dacryoadenitis.…”

Cathepsin S activation contributes to elevated CX3CL1 (fractalkine) levels in tears of a Sjögren’s syndrome murine model

“…S4) and using gene expression of inflammatory indicators in LG ( Supplementary Fig. S5), comparable to this previous characterization in male NOD mice over a comparable time period 8 , showed no indications of disease in the LG. As NOD mice develop diabetes in an age-and sex-dependent manner, a comprehensive evaluation of age-related blood-glucose levels in a previous cohort of male NOD mice also showed that no mice evaluated between 1 to 6 months of age had non-diabetic blood-glucose levels (below 250 mg/dL 54 ) ( Supplementary Fig.…”

“…2B). While increased LGAC CTSS is clearly secreted apically 8,10 , its cellular overexpression is expected to increase its abundance in tissue interstitium through release at basolateral membranes. CTSS is normally present in all cell lysosomes and in late endosomes and lysosomes of professional antigen-presenting cells.…”

“…Mouse age and sex were carefully selected based on the ability to develop the autoimmune dacryoadenitis and reduced tear flow characteristic of SS with a low diabetic risk. Lymphocytic infiltration in the LG is significantly correlated with disease development 8 . Male NOD mice consistently develop ~20% infiltration of the LG by 16 weeks 8 , while female NOD mouse are reported in one study to develop less than 1% infiltration of the LG by 24 weeks 53 .…”