Cytotherapy · 2025
Single cell transcriptional profiling of monocytes from asthma patients show a predisposition for an inflammatory response.
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Goss Kyndal, Grant Melanie L, Guglani Lokesh, Miller Hannah, Woods Erik J, Caldwell Cherish, Fitzpatrick Anne M, Horwitz Edwin M
Аннотация
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.
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.