Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin
Abstract Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the “Psoriasis Trea...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-10-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41984-2 |
| _version_ | 1797557974366945280 |
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| author | Qian Xiao Joseph Mears Aparna Nathan Kazuyoshi Ishigaki Yuriy Baglaenko Noha Lim Laura A. Cooney Kristina M. Harris Mark S. Anderson David A. Fox Dawn E. Smilek James G. Krueger Soumya Raychaudhuri |
| author_facet | Qian Xiao Joseph Mears Aparna Nathan Kazuyoshi Ishigaki Yuriy Baglaenko Noha Lim Laura A. Cooney Kristina M. Harris Mark S. Anderson David A. Fox Dawn E. Smilek James G. Krueger Soumya Raychaudhuri |
| author_sort | Qian Xiao |
| collection | DOAJ |
| description | Abstract Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the “Psoriasis Treatment with Abatacept and Ustekinumab: A Study of Efficacy”(PAUSE) clinical trial (n = 101), we report 953 expression quantitative trait loci (eQTLs). Of those, 116 eQTLs have effect sizes that were modulated by local skin inflammation (eQTL interactions). By examining these eQTL genes (eGenes), we find that most are expressed in the skin tissue compartment, and a subset overlap with the NRF2 pathway. Indeed, the strongest eQTL interaction signal – rs1491377616-LCE3C – links a psoriasis risk locus with a gene specifically expressed in the epidermis. This eQTL study highlights the potential to use biospecimens from clinical trials to discover in vivo eQTL interactions with therapeutically relevant environmental variables. |
| first_indexed | 2024-03-10T17:23:50Z |
| format | Article |
| id | doaj.art-dbc9e298d8244b0593bbd1a55d0a25b0 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:23:50Z |
| publishDate | 2023-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-dbc9e298d8244b0593bbd1a55d0a25b02023-11-20T10:16:08ZengNature PortfolioNature Communications2041-17232023-10-0114111710.1038/s41467-023-41984-2Immunosuppression causes dynamic changes in expression QTLs in psoriatic skinQian Xiao0Joseph Mears1Aparna Nathan2Kazuyoshi Ishigaki3Yuriy Baglaenko4Noha Lim5Laura A. Cooney6Kristina M. Harris7Mark S. Anderson8David A. Fox9Dawn E. Smilek10James G. Krueger11Soumya Raychaudhuri12Center for Data Sciences, Brigham and Women’s HospitalCenter for Data Sciences, Brigham and Women’s HospitalCenter for Data Sciences, Brigham and Women’s HospitalCenter for Data Sciences, Brigham and Women’s HospitalCenter for Data Sciences, Brigham and Women’s HospitalImmune Tolerance Network, Diabetes Center, University of California, San FranciscoImmune Tolerance Network, Diabetes Center, University of California, San FranciscoImmune Tolerance Network, Diabetes Center, University of California, San FranciscoImmune Tolerance Network, Diabetes Center, University of California, San FranciscoDivision of Rheumatology, Department of Internal Medicine and Clinical Autoimmunity Center of Excellence, University of MichiganImmune Tolerance Network, Diabetes Center, University of California, San FranciscoLaboratory for Investigative Dermatology, The Rockefeller UniversityCenter for Data Sciences, Brigham and Women’s HospitalAbstract Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the “Psoriasis Treatment with Abatacept and Ustekinumab: A Study of Efficacy”(PAUSE) clinical trial (n = 101), we report 953 expression quantitative trait loci (eQTLs). Of those, 116 eQTLs have effect sizes that were modulated by local skin inflammation (eQTL interactions). By examining these eQTL genes (eGenes), we find that most are expressed in the skin tissue compartment, and a subset overlap with the NRF2 pathway. Indeed, the strongest eQTL interaction signal – rs1491377616-LCE3C – links a psoriasis risk locus with a gene specifically expressed in the epidermis. This eQTL study highlights the potential to use biospecimens from clinical trials to discover in vivo eQTL interactions with therapeutically relevant environmental variables.https://doi.org/10.1038/s41467-023-41984-2 |
| spellingShingle | Qian Xiao Joseph Mears Aparna Nathan Kazuyoshi Ishigaki Yuriy Baglaenko Noha Lim Laura A. Cooney Kristina M. Harris Mark S. Anderson David A. Fox Dawn E. Smilek James G. Krueger Soumya Raychaudhuri Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin Nature Communications |
| title | Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin |
| title_full | Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin |
| title_fullStr | Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin |
| title_full_unstemmed | Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin |
| title_short | Immunosuppression causes dynamic changes in expression QTLs in psoriatic skin |
| title_sort | immunosuppression causes dynamic changes in expression qtls in psoriatic skin |
| url | https://doi.org/10.1038/s41467-023-41984-2 |
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