Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps
IntroductionChronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa with distinct endotypes including type 2 (T2) high eosinophilic CRS with nasal polyps (eCRSwNP), T2 low non-eosinophilic CRS with nasal polyps (neCRSwNP), and CRS without nasal polyps (CRSsNP).MethodsG...
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1321560/full |
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| author | George X. Huang George X. Huang Michael V. Mandanas Sarah Djeddi Sarah Djeddi Sarah Djeddi Daniela Fernandez-Salinas Daniela Fernandez-Salinas Daniela Fernandez-Salinas Maria Gutierrez-Arcelus Maria Gutierrez-Arcelus Maria Gutierrez-Arcelus Nora A. Barrett Nora A. Barrett |
| author_facet | George X. Huang George X. Huang Michael V. Mandanas Sarah Djeddi Sarah Djeddi Sarah Djeddi Daniela Fernandez-Salinas Daniela Fernandez-Salinas Daniela Fernandez-Salinas Maria Gutierrez-Arcelus Maria Gutierrez-Arcelus Maria Gutierrez-Arcelus Nora A. Barrett Nora A. Barrett |
| author_sort | George X. Huang |
| collection | DOAJ |
| description | IntroductionChronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa with distinct endotypes including type 2 (T2) high eosinophilic CRS with nasal polyps (eCRSwNP), T2 low non-eosinophilic CRS with nasal polyps (neCRSwNP), and CRS without nasal polyps (CRSsNP).MethodsGiven the heterogeneity of disease, we hypothesized that assessment of single cell RNA sequencing (scRNA-seq) across this spectrum of disease would reveal connections between infiltrating and activated immune cells and the epithelial and stromal populations that reside in sinonasal tissue.ResultsHere we find increased expression of genes encoding glycolytic enzymes in epithelial cells (EpCs), stromal cells, and memory T-cell subsets from patients with eCRSwNP, as compared to healthy controls. In basal EpCs, this is associated with a program of cell motility and Rho GTPase effector expression. Across both stromal and immune subsets, glycolytic programming was associated with extracellular matrix interactions, proteoglycan generation, and collagen formation. Furthermore, we report increased cell-cell interactions between EpCs and stromal/immune cells in eCRSwNP compared to healthy control tissue, and we nominate candidate receptor-ligand pairs that may drive tissue remodeling.DiscussionThese findings support a role for glycolytic reprograming in T2-elicited tissue remodeling and implicate increased cellular crosstalk in eCRSwNP. |
| first_indexed | 2024-03-07T23:38:07Z |
| format | Article |
| id | doaj.art-2ecc9fc60589481e910d2344a75b0779 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T23:38:07Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2ecc9fc60589481e910d2344a75b07792024-02-20T04:46:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13215601321560Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polypsGeorge X. Huang0George X. Huang1Michael V. Mandanas2Sarah Djeddi3Sarah Djeddi4Sarah Djeddi5Daniela Fernandez-Salinas6Daniela Fernandez-Salinas7Daniela Fernandez-Salinas8Maria Gutierrez-Arcelus9Maria Gutierrez-Arcelus10Maria Gutierrez-Arcelus11Nora A. Barrett12Nora A. Barrett13Division of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United StatesDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, MA, United StatesDivision of Immunology, Boston Children’s Hospital, Boston, MA, United StatesDepartment of Pediatrics, Harvard Medical School, Boston, MA, United StatesBroad Institute of MIT and Harvard, Cambridge, MA, United StatesDivision of Immunology, Boston Children’s Hospital, Boston, MA, United StatesDepartment of Pediatrics, Harvard Medical School, Boston, MA, United StatesBroad Institute of MIT and Harvard, Cambridge, MA, United StatesDivision of Immunology, Boston Children’s Hospital, Boston, MA, United StatesDepartment of Pediatrics, Harvard Medical School, Boston, MA, United StatesBroad Institute of MIT and Harvard, Cambridge, MA, United StatesDivision of Allergy and Clinical Immunology, Brigham and Women’s Hospital, Boston, MA, United StatesDepartment of Medicine, Harvard Medical School, Boston, MA, United StatesIntroductionChronic rhinosinusitis (CRS) is a chronic inflammatory disease of the sinonasal mucosa with distinct endotypes including type 2 (T2) high eosinophilic CRS with nasal polyps (eCRSwNP), T2 low non-eosinophilic CRS with nasal polyps (neCRSwNP), and CRS without nasal polyps (CRSsNP).MethodsGiven the heterogeneity of disease, we hypothesized that assessment of single cell RNA sequencing (scRNA-seq) across this spectrum of disease would reveal connections between infiltrating and activated immune cells and the epithelial and stromal populations that reside in sinonasal tissue.ResultsHere we find increased expression of genes encoding glycolytic enzymes in epithelial cells (EpCs), stromal cells, and memory T-cell subsets from patients with eCRSwNP, as compared to healthy controls. In basal EpCs, this is associated with a program of cell motility and Rho GTPase effector expression. Across both stromal and immune subsets, glycolytic programming was associated with extracellular matrix interactions, proteoglycan generation, and collagen formation. Furthermore, we report increased cell-cell interactions between EpCs and stromal/immune cells in eCRSwNP compared to healthy control tissue, and we nominate candidate receptor-ligand pairs that may drive tissue remodeling.DiscussionThese findings support a role for glycolytic reprograming in T2-elicited tissue remodeling and implicate increased cellular crosstalk in eCRSwNP.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1321560/fullchronic rhinosinusitissingle cell RNA sequencingepitheliumglycolysisepithelial mesenchymal interaction |
| spellingShingle | George X. Huang George X. Huang Michael V. Mandanas Sarah Djeddi Sarah Djeddi Sarah Djeddi Daniela Fernandez-Salinas Daniela Fernandez-Salinas Daniela Fernandez-Salinas Maria Gutierrez-Arcelus Maria Gutierrez-Arcelus Maria Gutierrez-Arcelus Nora A. Barrett Nora A. Barrett Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps Frontiers in Immunology chronic rhinosinusitis single cell RNA sequencing epithelium glycolysis epithelial mesenchymal interaction |
| title | Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_full | Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_fullStr | Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_full_unstemmed | Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_short | Increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps |
| title_sort | increased glycolysis and cellular crosstalk in eosinophilic chronic rhinosinusitis with nasal polyps |
| topic | chronic rhinosinusitis single cell RNA sequencing epithelium glycolysis epithelial mesenchymal interaction |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1321560/full |
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