Single cell transcriptional profiling of monocytes from asthma patients show a predisposition for an inflammatory response

Background: Asthma is the most common chronic lung disorder among children and young adults worldwide. Standard of care therapies are only partially effective and have side effects. Despite highly effective new biologic therapies, ~10% of patients continue to be poorly controlled. Methods. We isolated monocytes from peripheral blood obtained from an asthma patient who received an infusion of interferon ?-activated mesenchymal stromal cells (?MSCs), before and at 15 and 35 days after the infusion. We similarly isolated blood monocytes from otherwise healthy subjects with asthma and healthy controls for comparison. We interrogated the monocyte samples with single cell RNA sequencing followed by data analysis using the Seurat pipeline. Findings: A single infusion of ?MSCs induced a profound change in circulating monocyte gene expression, including reduction of HLA Class I expression and reduction of gene expression associated with type 1 and type 3 interferon signaling. Further examination of CD14+ and CD16+ monocytes from asthma patients revealed higher expression of proinflammatory genes compared to healthy controls, most notably increased expression of interferon response pathway genes. Within the asthma patients, several viral and interferon response pathways were significantly enriched in severe versus mild asthma. Interpretation: Circulating monocytes from asthma patients may be intrinsically programmed with a dysregulated interferon response. Monocyte directed therapy may be beneficial, especially for patients who are poorly controlled on currently available therapy. Finally, our data suggest that additional studies of ?MSC therapy for patients with poorly controlled asthma is warranted. Overall design: scRNAseq of PBMC isolated from patients with asthma and healthy controls. Preliminary data include patient receiving gMSC infusion with scRNAseq conducted pre-infusion, 15 days and 35 days post-infusion.