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. Despite effective new biologic therapies, ∼10% of patients remain poorly controlled. Monocytes contribute to the proinflammatory milieu in asthmatic lungs but also suppress inflammation and promote tissue healing.

AIMS: Compare the transcriptome of blood monocytes in asthma patients and healthy controls and assess the impact of an infusion of interferon y-activated mesenchymal stromal cells (yMSCs) on the transcriptome of asthmatic monocytes.

METHODS

scRNA-seq was conducted on blood monocytes isolated from an asthma patient before and after an infusion of γMSCs, on blood monocytes from otherwise healthy subjects with asthma, and from healthy controls.

RESULTS

One infusion of γMSCs induced profound gene expression changes, including reduced expression of HLA Class I and interferon signaling genes. Monocytes from asthma patients revealed increased expression of interferon response genes compared to healthy controls. Several viral and interferon response pathways were significantly enriched in severe versus mild asthma.

CONCLUSIONS

Our data suggest that monocyte directed therapy may be beneficial in asthma, especially for patients who are poorly controlled on currently available therapy, and additional studies of γMSC therapy for patients with poorly controlled asthma are warranted.