A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease
Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Research
2024
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| _version_ | 1817931260783230976 |
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| author | Thomas, T Friedrich, M Rich-Griffin, C Pohin, M Agarwal, D Pakpoor, J Lee, C Tandon, R Rendek, A Aschenbrenner, D Jainarayanan, A Voda, A Siu, JHY Sanches-Peres, R Nee, E Sathananthan, D Kotliar, D Todd, P Kiourlappou, M Gartner, L Ilott, N Issa, F Hester, J Turner, J Mackerodt, J Marsden, B Taylor, S Coles, M Jostins-Dean, L Powrie, FM Travis, S Uhlig, HH Dendrou, CA Buckley, CD |
| author_facet | Thomas, T Friedrich, M Rich-Griffin, C Pohin, M Agarwal, D Pakpoor, J Lee, C Tandon, R Rendek, A Aschenbrenner, D Jainarayanan, A Voda, A Siu, JHY Sanches-Peres, R Nee, E Sathananthan, D Kotliar, D Todd, P Kiourlappou, M Gartner, L Ilott, N Issa, F Hester, J Turner, J Mackerodt, J Marsden, B Taylor, S Coles, M Jostins-Dean, L Powrie, FM Travis, S Uhlig, HH Dendrou, CA Buckley, CD |
| author_sort | Thomas, T |
| collection | OXFORD |
| description | Precision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases. |
| first_indexed | 2024-12-09T03:19:12Z |
| format | Journal article |
| id | oxford-uuid:cc3bf0ce-b9f1-42af-a0e6-eed4ba0a643b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:19:12Z |
| publishDate | 2024 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:cc3bf0ce-b9f1-42af-a0e6-eed4ba0a643b2024-10-29T20:15:40ZA longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cc3bf0ce-b9f1-42af-a0e6-eed4ba0a643bEnglishJisc Publications RouterNature Research2024Thomas, TFriedrich, MRich-Griffin, CPohin, MAgarwal, DPakpoor, JLee, CTandon, RRendek, AAschenbrenner, DJainarayanan, AVoda, ASiu, JHYSanches-Peres, RNee, ESathananthan, DKotliar, DTodd, PKiourlappou, MGartner, LIlott, NIssa, FHester, JTurner, JMackerodt, JMarsden, BTaylor, SColes, MJostins-Dean, LPowrie, FMTravis, SUhlig, HHDendrou, CABuckley, CDPrecision medicine in immune-mediated inflammatory diseases (IMIDs) requires a cellular understanding of treatment response. We describe a therapeutic atlas for Crohn’s disease (CD) and ulcerative colitis (UC) following adalimumab, an anti-tumour necrosis factor (anti-TNF) treatment. We generated ~1 million single-cell transcriptomes, organised into 109 cell states, from 216 gut biopsies (41 subjects), revealing disease-specific differences. A systems biology-spatial analysis identified granuloma signatures in CD and interferon (IFN)-response signatures localising to T cell aggregates and epithelial damage in CD and UC. Pretreatment differences in epithelial and myeloid compartments were associated with remission outcomes in both diseases. Longitudinal comparisons demonstrated disease progression in nonremission: myeloid and T cell perturbations in CD and increased multi-cellular IFN signalling in UC. IFN signalling was also observed in rheumatoid arthritis (RA) synovium with a lymphoid pathotype. Our therapeutic atlas represents the largest cellular census of perturbation with the most common biologic treatment, anti-TNF, across multiple inflammatory diseases. |
| spellingShingle | Thomas, T Friedrich, M Rich-Griffin, C Pohin, M Agarwal, D Pakpoor, J Lee, C Tandon, R Rendek, A Aschenbrenner, D Jainarayanan, A Voda, A Siu, JHY Sanches-Peres, R Nee, E Sathananthan, D Kotliar, D Todd, P Kiourlappou, M Gartner, L Ilott, N Issa, F Hester, J Turner, J Mackerodt, J Marsden, B Taylor, S Coles, M Jostins-Dean, L Powrie, FM Travis, S Uhlig, HH Dendrou, CA Buckley, CD A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease |
| title | A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease |
| title_full | A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease |
| title_fullStr | A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease |
| title_full_unstemmed | A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease |
| title_short | A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease |
| title_sort | longitudinal single cell atlas of anti tumour necrosis factor treatment in inflammatory bowel disease |
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