Single-cell RNA sequencing of circulating immune cells supports inhibition of TNFAIP3 and NFKBIA translation as psoriatic arthritis biomarkers
ObjectiveTo identify biomarkers that distinguish psoriatic arthritis (PsA) from cutaneous psoriasis without arthritis (PsC) and healthy controls (HC) using single cell RNA sequencing (scRNA-seq).MethodPeripheral blood mononuclear cell samples from three patients with PsA fulfilling CASPAR criteria,...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-02-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1483393/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825206743555112960 |
|---|---|
| author | Ameth N. Garrido Rohan Machhar Omar F. Cruz-Correa Darshini Ganatra Sarah Q. Crome Sarah Q. Crome Joan Wither Joan Wither Joan Wither Igor Jurisica Igor Jurisica Igor Jurisica Dafna D. Gladman Dafna D. Gladman Dafna D. Gladman |
| author_facet | Ameth N. Garrido Rohan Machhar Omar F. Cruz-Correa Darshini Ganatra Sarah Q. Crome Sarah Q. Crome Joan Wither Joan Wither Joan Wither Igor Jurisica Igor Jurisica Igor Jurisica Dafna D. Gladman Dafna D. Gladman Dafna D. Gladman |
| author_sort | Ameth N. Garrido |
| collection | DOAJ |
| description | ObjectiveTo identify biomarkers that distinguish psoriatic arthritis (PsA) from cutaneous psoriasis without arthritis (PsC) and healthy controls (HC) using single cell RNA sequencing (scRNA-seq).MethodPeripheral blood mononuclear cell samples from three patients with PsA fulfilling CASPAR criteria, three patients with PsC and two HC were profiled using scRNA-seq. Differentially expressed genes (DEGs) identified through scRNA-seq were validated on classical monocytes, and CD4+ and CD8+ T cell subsets derived from an independent cohort of patients using the NanoString nCounter® platform. Protein expression was measured in CD4+ and CD8+ T cells by immunoblotting.ResultsA total of 18 immune cell population clusters were identified. Across 18 cell clusters, we identified 234 DEGs. NFKBIA and TNFAIP3 were overexpressed in PsA vs HC and PsC patients. Immunoblotting of the proteins encoded in these genes (IκBα and A20, respectively) showed higher levels in PsA CD4+ T cells compared to HC. Conversely, lower levels were observed in PsA CD8+ T cell lysates compared to HC for both proteins.ConclusionThese results suggest that translation of TNFAIP3 and NFKBIA may be inhibited in PsA CD8+ T cells. This study provides insight into the cellular heterogeneity of PsA, showing that non-cell type specific expression of genes associated with the disease can be dysregulated through different mechanisms in distinct cell types. |
| format | Article |
| id | doaj-art-b404d40f755143ca8a62e2959a271fd7 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b404d40f755143ca8a62e2959a271fd72025-02-07T06:49:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14833931483393Single-cell RNA sequencing of circulating immune cells supports inhibition of TNFAIP3 and NFKBIA translation as psoriatic arthritis biomarkersAmeth N. Garrido0Rohan Machhar1Omar F. Cruz-Correa2Darshini Ganatra3Sarah Q. Crome4Sarah Q. Crome5Joan Wither6Joan Wither7Joan Wither8Igor Jurisica9Igor Jurisica10Igor Jurisica11Dafna D. Gladman12Dafna D. Gladman13Dafna D. Gladman14Gladman-Krembil PsA Research Program, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON, CanadaGladman-Krembil PsA Research Program, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON, CanadaGladman-Krembil PsA Research Program, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON, CanadaGladman-Krembil PsA Research Program, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON, CanadaAjmera Transplant Centre, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, CanadaDepartment of Immunology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaDepartment of Immunology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaSchroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON, CanadaDivision of Rheumatology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaOsteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute and Data Science Discovery Centre for Chronic Diseases, Krembil Research Institute, University Health Network, Toronto, ON, CanadaDepartments of Medical Biophysics and Computer Science, and Faculty of Dentistry, University of Toronto, Toronto, ON, CanadaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaGladman-Krembil PsA Research Program, Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON, CanadaSchroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, ON, CanadaDivision of Rheumatology, Faculty of Medicine, University of Toronto, Toronto, ON, CanadaObjectiveTo identify biomarkers that distinguish psoriatic arthritis (PsA) from cutaneous psoriasis without arthritis (PsC) and healthy controls (HC) using single cell RNA sequencing (scRNA-seq).MethodPeripheral blood mononuclear cell samples from three patients with PsA fulfilling CASPAR criteria, three patients with PsC and two HC were profiled using scRNA-seq. Differentially expressed genes (DEGs) identified through scRNA-seq were validated on classical monocytes, and CD4+ and CD8+ T cell subsets derived from an independent cohort of patients using the NanoString nCounter® platform. Protein expression was measured in CD4+ and CD8+ T cells by immunoblotting.ResultsA total of 18 immune cell population clusters were identified. Across 18 cell clusters, we identified 234 DEGs. NFKBIA and TNFAIP3 were overexpressed in PsA vs HC and PsC patients. Immunoblotting of the proteins encoded in these genes (IκBα and A20, respectively) showed higher levels in PsA CD4+ T cells compared to HC. Conversely, lower levels were observed in PsA CD8+ T cell lysates compared to HC for both proteins.ConclusionThese results suggest that translation of TNFAIP3 and NFKBIA may be inhibited in PsA CD8+ T cells. This study provides insight into the cellular heterogeneity of PsA, showing that non-cell type specific expression of genes associated with the disease can be dysregulated through different mechanisms in distinct cell types.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1483393/fullpsoriatic arthritispsoriasisscRNA-seqTNFAIP3NFKBIA |
| spellingShingle | Ameth N. Garrido Rohan Machhar Omar F. Cruz-Correa Darshini Ganatra Sarah Q. Crome Sarah Q. Crome Joan Wither Joan Wither Joan Wither Igor Jurisica Igor Jurisica Igor Jurisica Dafna D. Gladman Dafna D. Gladman Dafna D. Gladman Single-cell RNA sequencing of circulating immune cells supports inhibition of TNFAIP3 and NFKBIA translation as psoriatic arthritis biomarkers Frontiers in Immunology psoriatic arthritis psoriasis scRNA-seq TNFAIP3 NFKBIA |
| title | Single-cell RNA sequencing of circulating immune cells supports inhibition of TNFAIP3 and NFKBIA translation as psoriatic arthritis biomarkers |
| title_full | Single-cell RNA sequencing of circulating immune cells supports inhibition of TNFAIP3 and NFKBIA translation as psoriatic arthritis biomarkers |
| title_fullStr | Single-cell RNA sequencing of circulating immune cells supports inhibition of TNFAIP3 and NFKBIA translation as psoriatic arthritis biomarkers |
| title_full_unstemmed | Single-cell RNA sequencing of circulating immune cells supports inhibition of TNFAIP3 and NFKBIA translation as psoriatic arthritis biomarkers |
| title_short | Single-cell RNA sequencing of circulating immune cells supports inhibition of TNFAIP3 and NFKBIA translation as psoriatic arthritis biomarkers |
| title_sort | single cell rna sequencing of circulating immune cells supports inhibition of tnfaip3 and nfkbia translation as psoriatic arthritis biomarkers |
| topic | psoriatic arthritis psoriasis scRNA-seq TNFAIP3 NFKBIA |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1483393/full |
| work_keys_str_mv | AT amethngarrido singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT rohanmachhar singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT omarfcruzcorrea singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT darshiniganatra singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT sarahqcrome singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT sarahqcrome singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT joanwither singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT joanwither singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT joanwither singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT igorjurisica singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT igorjurisica singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT igorjurisica singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT dafnadgladman singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT dafnadgladman singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers AT dafnadgladman singlecellrnasequencingofcirculatingimmunecellssupportsinhibitionoftnfaip3andnfkbiatranslationaspsoriaticarthritisbiomarkers |