STING Mediates Lupus Via the Activation of Conventional Dendritic Cell Maturation and Plasmacytoid Dendritic Cell Differentiation

Overview

Journal iScience

Publisher Cell Press

Date 2020 Oct 21

PMID 33083760

Citations 36

Authors

Arthid Thim-Uam

Thaneas Prabakaran

Mookmanee Tansakul

Jiradej Makjaroen

Piriya Wongkongkathep

Naphat Chantaravisoot

Thammakorn Saethang

Asada Leelahavanichkul

Thitima Benjachat

Soren Paludan

Trairak Pisitkun

Prapaporn Pisitkun

Affiliations

Soon will be listed here.

Abstract

Signaling through stimulator of interferon genes (STING) leads to the production of type I interferons (IFN-Is) and inflammatory cytokines. A gain-of-function mutation in STING was identified in an autoinflammatory disease (STING-associated vasculopathy with onset in infancy; SAVI). The expression of cyclic GMP-AMP, DNA-activated cGAS-STING pathway, increased in a proportion of patients with SLE. The STING signaling pathway may be a candidate for targeted therapy in SLE. Here, we demonstrated that disruption of STING signaling ameliorated lupus development in -deficient mice. Activation of STING promoted maturation of conventional dendritic cells and differentiation of plasmacytoid dendritic cells via LYN interaction and phosphorylation. The inhibition of LYN decreased the differentiation of STING-activated dendritic cells. Adoptive transfer of STING-activated bone marrow-derived dendritic cells into the FCGR2B and STING double-deficiency mice restored lupus phenotypes. These findings provide evidence that the inhibition of STING signaling may be a candidate targeted treatment for a subset of patients with SLE.

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