| Title: |
CCR4+ CD8+ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis |
| Authors: |
Montico, Guendalina; Mingozzi, Francesca; Casciano, Fabio; Protti, Giulia; Gornati, Laura; Marzola, Erika; Banfi, Giuseppe; Guerrini, Remo; Secchiero, Paola; Volinia, Stefano; Granucci, Francesca; Reali, Eva |
| Contributors: |
Montico, Guendalina; Mingozzi, Francesca; Casciano, Fabio; Protti, Giulia; Gornati, Laura; Marzola, Erika; Banfi, Giuseppe; Guerrini, Remo; Secchiero, Paola; Volinia, Stefano; Granucci, Francesca; Reali, Eva |
| Publisher Information: |
John Wiley and Sons Inc |
| Publication Year: |
2023 |
| Subject Terms: |
Clonal expansion; Chemokine receptors; Psoriasis and psoriatic arthritis; Self-reactive CD8 T cells; T-cell recirculation |
| Description: |
Psoriasis is a chronic inflammatory skin disease with an autoimmune component and associated with joint inflammation in up to 30% of cases. To investigate autoreactive T cells, we developed an imiquimod-induced psoriasis-like inflammation model in K5-mOVA.tg C57BL/6 mice expressing ovalbumin (OVA) on the keratinocyte membrane, adoptively transferred with OT-I OVA-specific CD8(+) T cells. We evaluated the expansion of OT-I CD8(+) T cells and their localization in skin, blood, and spleen. scRNA-seq and TCR sequencing data from patients with psoriatic arthritis were also analyzed. In the imiquimod-treated K5-mOVA.tg mouse model, OT-I T cells were markedly expanded in the skin and blood at early time points. OT-I T cells in the skin showed mainly CXCR3(+) effector memory phenotype, whereas in peripheral blood there was an expansion of CCR4(+)CXCR3(+) OT-I cells. At a later time point, expanded OVA-specific T-cell population was found in the spleen. In patients with psoriatic arthritis, scRNA-seq and TCR sequencing data showed clonal expansion of CCR4(+) T-CM cells in the circulation and further expansion in the synovial fluid. Importantly, there was a clonotype overlap between CCR4(+) T-CM in the peripheral blood and CD8(+) T-cell effectors in the synovial fluid. This mechanism could play a role in the generation and spreading of autoreactive T cells to the synovioentheseal tissues in psoriasis patients at risk of developing psoriatic arthritis. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/36722608; info:eu-repo/semantics/altIdentifier/wos/WOS:000936702200001; volume:53; issue:4; numberofpages:13; journal:EUROPEAN JOURNAL OF IMMUNOLOGY; https://hdl.handle.net/20.500.11768/174278 |
| DOI: |
10.1002/eji.202149702 |
| Availability: |
https://hdl.handle.net/20.500.11768/174278; https://doi.org/10.1002/eji.202149702; https://onlinelibrary.wiley.com/doi/10.1002/eji.202149702 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.44F69DED |
| Database: |
BASE |