Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris
Psoriasis vulgaris (PV) is a chronic, recurrent inflammatory dermatosis mediated by aberrantly activated immune cells. The role of the innate-like T cells, particularly gammadelta T (γδT) cells and MR1-restricted T lymphocytes, is incompletely explored, mainly through animal models, or by use of sur...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.572924/full |
| _version_ | 1818648797057646592 |
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| author | Vera Plužarić Vera Plužarić Mario Štefanić Martina Mihalj Martina Mihalj Maja Tolušić Levak Maja Tolušić Levak Ivanka Muršić Ljubica Glavaš-Obrovac Martin Petrek Peter Balogh Stana Tokić |
| author_facet | Vera Plužarić Vera Plužarić Mario Štefanić Martina Mihalj Martina Mihalj Maja Tolušić Levak Maja Tolušić Levak Ivanka Muršić Ljubica Glavaš-Obrovac Martin Petrek Peter Balogh Stana Tokić |
| author_sort | Vera Plužarić |
| collection | DOAJ |
| description | Psoriasis vulgaris (PV) is a chronic, recurrent inflammatory dermatosis mediated by aberrantly activated immune cells. The role of the innate-like T cells, particularly gammadelta T (γδT) cells and MR1-restricted T lymphocytes, is incompletely explored, mainly through animal models, or by use of surrogate lineage markers, respectively. Here, we used case-control settings, multiparameter flow cytometry, 5-OP-RU-loaded MR1-tetramers, Luminex technology and targeted qRT-PCR to dissect the cellular and transcriptional landscape of γδ and MR1-restricted blood T cells in untreated PV cases (n=21, 22 matched controls). High interpersonal differences in cell composition were observed, fueling transcriptional variability at healthy baseline. A minor subset of canonical CD4+CD8+MR1-tet+TCRVα7.2+ and CD4+CD8-MR1-tet+TCRVα7.2+ T cells was the most significantly underrepresented community in male PV individuals, whereas Vδ2+ γδ T cells expressing high levels of TCR and Vδ1-δ2- γδ T cells expressing intermediate levels of TCR were selectively enriched in affected males, partly reflecting disease severity. Our findings highlight a formerly unappreciated skewing of human circulating MAIT and γδ cytomes during PV, and reveal their compositional changes in relation to sex, CMV exposure, serum cytokine content, BMI, and inflammatory burden. Complementing numerical alterations, we finally show that flow-sorted, MAIT and γδ populations exhibit divergent transcriptional changes in mild type I psoriasis, consisting of differential bulk expression for signatures of cytotoxicity/type-1 immunity (EOMES, RUNX3, IL18R), type-3 immunity (RORC, CCR6), and T cell innateness (ZBTB16). |
| first_indexed | 2024-12-17T01:24:08Z |
| format | Article |
| id | doaj.art-73831b80964c491a8d96e392809476d4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T01:24:08Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-73831b80964c491a8d96e392809476d42022-12-21T22:08:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-12-011110.3389/fimmu.2020.572924572924Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis VulgarisVera Plužarić0Vera Plužarić1Mario Štefanić2Martina Mihalj3Martina Mihalj4Maja Tolušić Levak5Maja Tolušić Levak6Ivanka Muršić7Ljubica Glavaš-Obrovac8Martin Petrek9Peter Balogh10Stana Tokić11Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Osijek, Osijek, CroatiaDepartment of Dermatology and Venerology, University Hospital Osijek, Osijek, CroatiaDepartment of Nuclear Medicine and Oncology, Faculty of Medicine, University of Osijek, Osijek, CroatiaDepartment of Dermatology and Venerology, University Hospital Osijek, Osijek, CroatiaDepartment of Physiology and Immunology, Faculty of Medicine, University of Osijek, Osijek, CroatiaDepartment of Dermatology and Venerology, University Hospital Osijek, Osijek, CroatiaDepartment of Histology and Embryology, Faculty of Medicine, University of Osijek, Osijek, CroatiaDepartment of Dermatology and Venerology, University Hospital Osijek, Osijek, CroatiaDepartment of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Osijek, Osijek, CroatiaDepartment of Pathological Physiology, Faculty of Medicine and Dentistry, Palacký University, Olomouc, CzechiaDepartment of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, Pecs, HungaryDepartment of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Osijek, Osijek, CroatiaPsoriasis vulgaris (PV) is a chronic, recurrent inflammatory dermatosis mediated by aberrantly activated immune cells. The role of the innate-like T cells, particularly gammadelta T (γδT) cells and MR1-restricted T lymphocytes, is incompletely explored, mainly through animal models, or by use of surrogate lineage markers, respectively. Here, we used case-control settings, multiparameter flow cytometry, 5-OP-RU-loaded MR1-tetramers, Luminex technology and targeted qRT-PCR to dissect the cellular and transcriptional landscape of γδ and MR1-restricted blood T cells in untreated PV cases (n=21, 22 matched controls). High interpersonal differences in cell composition were observed, fueling transcriptional variability at healthy baseline. A minor subset of canonical CD4+CD8+MR1-tet+TCRVα7.2+ and CD4+CD8-MR1-tet+TCRVα7.2+ T cells was the most significantly underrepresented community in male PV individuals, whereas Vδ2+ γδ T cells expressing high levels of TCR and Vδ1-δ2- γδ T cells expressing intermediate levels of TCR were selectively enriched in affected males, partly reflecting disease severity. Our findings highlight a formerly unappreciated skewing of human circulating MAIT and γδ cytomes during PV, and reveal their compositional changes in relation to sex, CMV exposure, serum cytokine content, BMI, and inflammatory burden. Complementing numerical alterations, we finally show that flow-sorted, MAIT and γδ populations exhibit divergent transcriptional changes in mild type I psoriasis, consisting of differential bulk expression for signatures of cytotoxicity/type-1 immunity (EOMES, RUNX3, IL18R), type-3 immunity (RORC, CCR6), and T cell innateness (ZBTB16).https://www.frontiersin.org/articles/10.3389/fimmu.2020.572924/fullpsoriasiscytokinesgammadelta T lymphocytesmucosal associated invariant T cellsMR1 |
| spellingShingle | Vera Plužarić Vera Plužarić Mario Štefanić Martina Mihalj Martina Mihalj Maja Tolušić Levak Maja Tolušić Levak Ivanka Muršić Ljubica Glavaš-Obrovac Martin Petrek Peter Balogh Stana Tokić Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris Frontiers in Immunology psoriasis cytokines gammadelta T lymphocytes mucosal associated invariant T cells MR1 |
| title | Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris |
| title_full | Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris |
| title_fullStr | Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris |
| title_full_unstemmed | Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris |
| title_short | Differential Skewing of Circulating MR1-Restricted and γδ T Cells in Human Psoriasis Vulgaris |
| title_sort | differential skewing of circulating mr1 restricted and γδ t cells in human psoriasis vulgaris |
| topic | psoriasis cytokines gammadelta T lymphocytes mucosal associated invariant T cells MR1 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.572924/full |
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