IL-6 receptor blockade corrects defects of XIAP-deficient regulatory T cells.

ABSTRACT: X-linked lymphoproliferative syndrome type-2 (XLP-2) is a primary immunodeficiency disease attributed to XIAP mutation and is triggered by infection. Here, we show that mouse Xiap^-/- regulatory T (Treg) cells and human XIAP-deficient Treg cells are defective in suppressive function. The Xiap^-/- Treg cell defect is linked partly to decreased SOCS1 expression. XIAP binds SOCS1 and promotes SOCS1 stabilization. Foxp3 stability is reduced in Xiap^-/- Treg cells. In addition, Xiap^-/- Treg cells are prone to IFN-γ secretion. Transfer of wild-type Treg cells partly rescues infection-induced inflammation in Xiap^-/- mice. Notably, inflammation-induced reprogramming of Xiap^-/- Treg cells can be prevented by blockade of the IL-6 recepto

SUBMITTER: Hsieh WC 

PROVIDER: S-EPMC5792625 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature