The soluble CTLA-4 splice variant protects from type 1 diabetes and potentiates regulatory T-cell function.

ABSTRACT:

Objective

CTLA4 gene variation associates with multiple autoimmune disorders, including type 1 diabetes. The CTLA4 susceptibility allele was found to generate decreased levels of mRNA encoding soluble CTLA-4 (sCTLA-4) relative to the full-length isoform, the functional consequence of which is as yet unknown. In this study, we investigated the contribution of sCTLA-4 to immune regulation with the aim to elucidate the functional basis of the disease association of CTLA4.

Research design and methods

To model the disease-associated splicing variation of CTLA4, we generated NOD mice in which sCTLA-4 mRNA is silenced by RNA interference.

Results

We found that loss of sCTLA-4 impairs the function of regulatory T (Treg) cells. This functional defect could be attributed, at le

SUBMITTER: Gerold KD 

PROVIDER: S-EPMC3121435 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature