Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics
Abstract Patients with severe eosinophilic asthma often require systemic medication, including corticosteroids and anti-type 2 (T2) cytokine biologics, to control the disease. While anti-IL5 and anti-IL4Rα antibodies suppress the effects of IL-4, IL-5 and IL-13, the molecular pathways modified by th...
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Nature Publishing Group
2024-12-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01368-y |
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| author | Kyungtaek Park Ji-Hyang Lee Eunsoon Shin Hye Yoon Jang Woo-Jung Song Hyouk-Soo Kwon Yoo Sook Cho Jong Eun Lee Ian Adcock Kian Fan Chung Jeong Seok Lee Sungho Won Tae-Bum Kim |
| author_facet | Kyungtaek Park Ji-Hyang Lee Eunsoon Shin Hye Yoon Jang Woo-Jung Song Hyouk-Soo Kwon Yoo Sook Cho Jong Eun Lee Ian Adcock Kian Fan Chung Jeong Seok Lee Sungho Won Tae-Bum Kim |
| author_sort | Kyungtaek Park |
| collection | DOAJ |
| description | Abstract Patients with severe eosinophilic asthma often require systemic medication, including corticosteroids and anti-type 2 (T2) cytokine biologics, to control the disease. While anti-IL5 and anti-IL4Rα antibodies suppress the effects of IL-4, IL-5 and IL-13, the molecular pathways modified by these biologics that are associated with clinical improvement remain unclear. Therefore, we aimed to describe the effects of T2-targeting biologics on the gene expression of blood immune cells. We conducted single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from eight patients with severe eosinophilic asthma treated with mepolizumab, reslizumab, or dupilumab. PBMCs were obtained before the initiation of biologics and at 1- and 6-month timepoints after the initiation of treatment to elucidate treatment-induced changes. During treatment, the proportions of T cells/natural killer (NK) cells, myeloid cells, and B cells did not change. However, the composition of classical monocytes (CMs) changed: IL1B + CMs were reduced, and S100A + CMs were increased. The subsets of T cells also changed, and significant downregulation of the NF-κB pathway was observed. The genes related to the NF-κB pathway were suppressed across T/NK, myeloid, and B cells. The transcriptional landscape did not significantly change after the first month of treatment, but marked changes occurred at six-month intervals. In conclusion, regardless of the type of biologics used, suppression of T2-mediated pathways ultimately reduces the expression of genes related to NF-κB signaling in circulating immune cells. Further studies are warranted to identify potential biomarkers related to treatment response and long-term outcomes. Clinical trial registration number: NCT05164939 |
| format | Article |
| id | doaj-art-85ba9202acb244e6a5ca118e7d6e36bc |
| institution | DOAJ |
| issn | 2092-6413 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-85ba9202acb244e6a5ca118e7d6e36bc2025-08-20T02:43:24ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132024-12-0156122755276210.1038/s12276-024-01368-ySingle-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologicsKyungtaek Park0Ji-Hyang Lee1Eunsoon Shin2Hye Yoon Jang3Woo-Jung Song4Hyouk-Soo Kwon5Yoo Sook Cho6Jong Eun Lee7Ian Adcock8Kian Fan Chung9Jeong Seok Lee10Sungho Won11Tae-Bum Kim12Institute of Health and Environment, Seoul National UniversityDepartment of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of MedicineDNA Link, Inc, Seodaemun-Gu Bugahyeon-Ro 150DNA Link, Inc, Seodaemun-Gu Bugahyeon-Ro 150Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of MedicineDepartment of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of MedicineDNA Link, Inc, Seodaemun-Gu Bugahyeon-Ro 150National Heart and Lung Institute, Imperial College LondonNational Heart and Lung Institute, Imperial College LondonGenome Insight, Inc., San DiegoInstitute of Health and Environment, Seoul National UniversityDepartment of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of MedicineAbstract Patients with severe eosinophilic asthma often require systemic medication, including corticosteroids and anti-type 2 (T2) cytokine biologics, to control the disease. While anti-IL5 and anti-IL4Rα antibodies suppress the effects of IL-4, IL-5 and IL-13, the molecular pathways modified by these biologics that are associated with clinical improvement remain unclear. Therefore, we aimed to describe the effects of T2-targeting biologics on the gene expression of blood immune cells. We conducted single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from eight patients with severe eosinophilic asthma treated with mepolizumab, reslizumab, or dupilumab. PBMCs were obtained before the initiation of biologics and at 1- and 6-month timepoints after the initiation of treatment to elucidate treatment-induced changes. During treatment, the proportions of T cells/natural killer (NK) cells, myeloid cells, and B cells did not change. However, the composition of classical monocytes (CMs) changed: IL1B + CMs were reduced, and S100A + CMs were increased. The subsets of T cells also changed, and significant downregulation of the NF-κB pathway was observed. The genes related to the NF-κB pathway were suppressed across T/NK, myeloid, and B cells. The transcriptional landscape did not significantly change after the first month of treatment, but marked changes occurred at six-month intervals. In conclusion, regardless of the type of biologics used, suppression of T2-mediated pathways ultimately reduces the expression of genes related to NF-κB signaling in circulating immune cells. Further studies are warranted to identify potential biomarkers related to treatment response and long-term outcomes. Clinical trial registration number: NCT05164939https://doi.org/10.1038/s12276-024-01368-y |
| spellingShingle | Kyungtaek Park Ji-Hyang Lee Eunsoon Shin Hye Yoon Jang Woo-Jung Song Hyouk-Soo Kwon Yoo Sook Cho Jong Eun Lee Ian Adcock Kian Fan Chung Jeong Seok Lee Sungho Won Tae-Bum Kim Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics Experimental and Molecular Medicine |
| title | Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics |
| title_full | Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics |
| title_fullStr | Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics |
| title_full_unstemmed | Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics |
| title_short | Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics |
| title_sort | single cell rna sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics |
| url | https://doi.org/10.1038/s12276-024-01368-y |
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