Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma
Abstract Pediatric obesity-related asthma is characterized by non-atopic T helper 1 (Th1) inflammation and steroid resistance. CDC42 upregulation in CD4 + T cells underlies Th1 inflammation but the CD4 + T cell subtype(s) with CDC42 upregulation and their contribution to steroid resistance are not k...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-88423-4 |
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| author | David A. Thompson Yvonne B. Wabara Sarai Duran Anna Reichenbach Laura Chen Kayla Collado Changsuek Yon John M. Greally DMed Deepa Rastogi |
| author_facet | David A. Thompson Yvonne B. Wabara Sarai Duran Anna Reichenbach Laura Chen Kayla Collado Changsuek Yon John M. Greally DMed Deepa Rastogi |
| author_sort | David A. Thompson |
| collection | DOAJ |
| description | Abstract Pediatric obesity-related asthma is characterized by non-atopic T helper 1 (Th1) inflammation and steroid resistance. CDC42 upregulation in CD4 + T cells underlies Th1 inflammation but the CD4 + T cell subtype(s) with CDC42 upregulation and their contribution to steroid resistance are not known. Compared to healthy-weight asthma, obesity-alone and healthy-weight controls, single-cell transcriptomics of obese asthma CD4 + T cells revealed CDC42 upregulation in 3 clusters comprised of naïve and central memory T cells, which differed from the cluster enriched for Th1 responses that was comprised of effector T cells. NR3C1, coding for the glucocorticoid receptor, was downregulated, while genes coding for NLRP3 inflammasome were upregulated, in clusters with CDC42 upregulation and Th1 responses. Conserved genes in these clusters correlated with pulmonary function deficits in obese asthma. These findings suggest that several distinct CD4 + T cell subtypes are programmed in obese asthma for CDC42 upregulation, Th1 inflammation, and steroid resistance, and together contribute to the obese asthma phenotype. |
| format | Article |
| id | doaj-art-a6ffd186aa534647af5247f2ed7cb878 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a6ffd186aa534647af5247f2ed7cb8782025-08-20T03:04:16ZengNature PortfolioScientific Reports2045-23222025-02-0115111710.1038/s41598-025-88423-4Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthmaDavid A. Thompson0Yvonne B. Wabara1Sarai Duran2Anna Reichenbach3Laura Chen4Kayla Collado5Changsuek Yon6John M. Greally DMed7Deepa Rastogi8Department of Pediatrics, Albert Einstein College of MedicineChildren’s National Hospital, George Washington UniversityDepartment of Pediatrics, Albert Einstein College of MedicineDepartment of Pediatrics, Albert Einstein College of MedicineDepartment of Pediatrics, Yale UniversityMontefiore Health System, Albert Einstein College of MedicineDepartment of Pediatrics, Albert Einstein College of MedicineDepartment of Pediatrics, Albert Einstein College of MedicineDepartment of Pediatrics, Albert Einstein College of MedicineAbstract Pediatric obesity-related asthma is characterized by non-atopic T helper 1 (Th1) inflammation and steroid resistance. CDC42 upregulation in CD4 + T cells underlies Th1 inflammation but the CD4 + T cell subtype(s) with CDC42 upregulation and their contribution to steroid resistance are not known. Compared to healthy-weight asthma, obesity-alone and healthy-weight controls, single-cell transcriptomics of obese asthma CD4 + T cells revealed CDC42 upregulation in 3 clusters comprised of naïve and central memory T cells, which differed from the cluster enriched for Th1 responses that was comprised of effector T cells. NR3C1, coding for the glucocorticoid receptor, was downregulated, while genes coding for NLRP3 inflammasome were upregulated, in clusters with CDC42 upregulation and Th1 responses. Conserved genes in these clusters correlated with pulmonary function deficits in obese asthma. These findings suggest that several distinct CD4 + T cell subtypes are programmed in obese asthma for CDC42 upregulation, Th1 inflammation, and steroid resistance, and together contribute to the obese asthma phenotype.https://doi.org/10.1038/s41598-025-88423-4ObesityAsthmaCD4 + T cellsChildren |
| spellingShingle | David A. Thompson Yvonne B. Wabara Sarai Duran Anna Reichenbach Laura Chen Kayla Collado Changsuek Yon John M. Greally DMed Deepa Rastogi Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma Scientific Reports Obesity Asthma CD4 + T cells Children |
| title | Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma |
| title_full | Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma |
| title_fullStr | Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma |
| title_full_unstemmed | Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma |
| title_short | Single cell analysis identifies distinct CD4 + T cells associated with the pathobiology of pediatric obesity related asthma |
| title_sort | single cell analysis identifies distinct cd4 t cells associated with the pathobiology of pediatric obesity related asthma |
| topic | Obesity Asthma CD4 + T cells Children |
| url | https://doi.org/10.1038/s41598-025-88423-4 |
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