Cathepsin L inhibition prevents murine autoimmune diabetes via suppression of CD8(+) T cell activity.

ABSTRACT:

Background

Type 1 diabetes (T1D) is an autoimmune disease resulting from defects in central and peripheral tolerance and characterized by T cell-mediated destruction of islet β cells. To determine whether specific lysosomal proteases might influence the outcome of a T cell-mediated autoimmune response, we examined the functional significance of cathepsin inhibition on autoimmune T1D-prone non-obese diabetic (NOD) mice.

Methods and findings

Here it was found that specific inhibition of cathepsin L affords strong protection from cyclophosphamide (CY)-induced insulitis and diabetes of NOD mice at the advanced stage of CD8(+) T cell infiltration via inhibiting granzyme activity. It was discovered that cathepsin L inhibition prevents cytotoxic activity of CD8(+) T cells in the pa

SUBMITTER: Yamada A 

PROVIDER: S-EPMC2943924 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature