Stanniocalcin-2 contributes to mesenchymal stromal cells attenuating murine contact hypersensitivity mainly via reducing CD8+ Tc1 cells

Cell Death & Disease
Xiaoyong ChenQi Zhang

Abstract

Mesenchymal stromal cells (MSCs) have been demonstrated to ameliorate allergic contact dermatitis (ACD), a typical T-cell-mediated disorder. However, the underlying mechanisms behind the MSC-based treatment for ACD have not yet been fully elucidated. The stanniocalcins (STCs) comprise a family of secreted glycoprotein hormones that act as important anti-inflammatory proteins. Here, we investigated the roles of STCs in MSC-mediated T-cell suppression and their potential role in the MSC-based treatment for ACD. Gene expression profiling revealed that STC2, but not STC1, was highly expressed in MSCs. STC2 knockdown in MSCs significantly impaired their effects in reducing TNF-α- and IFN-γ-producing CD8+ T cells. Importantly, silencing the STC2 expression in MSCs abated their therapeutic effect on contact hypersensitivity (CHS) in mice, mainly restoring the generation and infiltration of IFN-γ-producing CD8+ T cells (Tc1 cells). Mechanistically, STC2 co-localized with heme oxygenase 1 (HO-1) in MSCs, and contributed to MSC-mediated reduction of CD8+ Tc1 cells via regulating HO-1 activity. Together, these findings newly identify STC2 as the first stanniocalcin responsible for mediating the immunomodulatory effects of MSCs on allogene...Continue Reading

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Citations

Sep 10, 2020·International Journal of Molecular Sciences·Anna WajdaAgnieszka Paradowska-Gorycka
Aug 26, 2019·Allergology International : Official Journal of the Japanese Society of Allergology·He LiWenru Su
Jul 28, 2020·Current Stem Cell Research & Therapy·Wang GongQianming Chen

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Methods Mentioned

BETA
flow cytometry
ELISA
co-immunoprecipitation
super-resolution microscopy
transfection
density gradient centrifugation
PMA
PCR

Software Mentioned

Kaluza
ImageJ
Prism

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