Bone marrow mesenchymal stem cells from patients with SLE maintain an interferon signature during in vitro culture.

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 ß-galactosidase. We have also shown SLE BMSC produce increased amounts of interferon beta (IFNß), have increased mRNA for several genes induced by IFNß, 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 IFNß by ELISA. RESULTS: On the basis of top differentially expressed genes between SLE and healthy controls, SLE patients with high levels of serum IFNß clustered together while SLE patients with low levels of IFNß 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 IFNß high subjects, per se. Moreover, gene expression changes induced by treating healthy BMSC with exogenous IFNß were remarkably similar to gene expression differences in SLE IFNß 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 IFNß in vivo.

Effect of aging on cytokine production in response to respiratory syncytial virus infection.

In vitro cytokine production in response to respiratory syncytial virus (RSV) and influenza infections was investigated in 11 "young" (mean age, 31 years) and "older" (mean age, 75 years) healthy volunteers by use of interferon (IFN)-gamma ELISPOT and ELISA analysis of cytokines in culture supernatants. Autologous dendritic cells (DCs), derived by culturing adherent peripheral blood mononuclear cells in granulocyte-macrophage colony--stimulating factor and interleukin-4, were used as antigen-presenting cells. Older subjects produced significantly fewer IFN-gamma ELISPOTs in response to RSV than the younger subjects. These results suggest that aging may be associated with a defect in the T cell response to RSV, even when DCs are used to maximize costimulation. This defect in cellular immunity may be related to the increased morbidity observed with RSV infection in elderly persons.