Bone marrow mesenchymal stem cells from patients with SLE maintain an interferon signature during in vitro culture. (August 2020) - Gao, Lin
Highlights: SLE BMSC grown in vitro have a type I interferon signature. The type I interferon signatures of SLE BMSC is a form of in vivo imprinting. Serum levels in IFNβ correlated with the interferon signature of SLE BMSC. A subset of lupus patients had normal serum IFNβ and no interferon signature in BMSC. Abstract: Background: We have previously shown that SLE BMSC have decreased proliferation, increased ROS, increased DNA damage and repair (DDR), a senescence associated secretory phenotype, and increased senescence-associated β-galactosidase. We have also shown SLE BMSC produce increased amounts of interferon beta (IFNβ), have increased mRNA for several genes induced by IFNβ, and have a pro-inflammatory feedback loop mediated by a MAVS. To better understand the phenotype of SLE BMSC we conducted mRNA sequencing. Methods: Patients fulfilling SLE classification criteria and age and sex matched healthy controls were recruited under an Institutional Review Board approved protocol. Bone marrow aspirates and peripheral blood samples were obtained. BMSC were isolated and grown in tissue culture. Early passage BMSC were harvested and mRNA samples were sent for RNAseq. Serum samples were assayed for IFNβ by ELISA. Results: On the basis of top differentially expressed genes between SLE and healthy controls, SLE patients with high levels of serum IFNβ clustered together while SLE patients with low levels of IFNβ clustered with healthy controls. Those genes differentially expressed in SLE patients generally belonged to known IFN pathways, and showed a strong overlap with the set of genes differentially expressed in IFNβ high subjects, per se. Moreover, gene expression changes induced by treating healthy BMSC with exogenous IFNβ were remarkably similar to gene expression differences in SLE IFNβ high vs low BMSC. Conclusions: BMSCs from SLE patients are heterogeneous. A subgroup of SLE BMSC is distinguished from other SLE BMSC and from controls by increased levels of mRNAs induced by type I interferons. This subgroup of SLE patients had increased levels of IFNβ in vivo.