Unknown

Dataset Information

0

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-? 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 receptor (IL-6R), and a combination of anti-IL-6R and Xiap-/- Treg cells confers survival to inflammatory infection in Xiap-/- mice. Our results suggest that XLP-2 can be corrected by combination treatment with autologous iTreg (induced Treg) cells and anti-IL-6R antibody, bypassing the necessity to transduce Treg cells with XIAP.

SUBMITTER: Hsieh WC 

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

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Hsieh Wan-Chen WC   Hsu Tzu-Sheng TS   Chang Ya-Jen YJ   Lai Ming-Zong MZ  

Nature communications 20180131 1


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<sup>-/-</sup> regulatory T (Treg) cells and human XIAP-deficient Treg cells are defective in suppressive function. The Xiap<sup>-/-</sup> Treg cell defect is linked partly to decreased SOCS1 expression. XIAP binds SOCS1 and promotes SOCS1 stabilization. Foxp3 stability is reduced in Xiap<sup>-/-</sup> Treg cells. In ad  ...[more]

Similar Datasets

| S-EPMC3175779 | biostudies-literature
| S-EPMC4246063 | biostudies-literature
| S-EPMC479745 | biostudies-literature
| S-EPMC8304158 | biostudies-literature
| S-EPMC3943944 | biostudies-literature
| S-EPMC7153846 | biostudies-literature
| S-EPMC8636116 | biostudies-literature
| S-EPMC2842445 | biostudies-literature
| S-EPMC7144868 | biostudies-literature
| S-EPMC3411948 | biostudies-literature