CCR4+ CD8+ T cells clonally expand to differentiated effectors in murine psoriasis and in human psoriatic arthritis.

Abstract

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+ TCM cells in the circulation and further expansion in the synovial fluid. Importantly, there was a clonotype overlap between CCR4+ TCM 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.

• Authors: Guendalina Montico, Francesca Mingozzi, Fabio Casciano, Giulia Protti, Laura Gornati, Erika Marzola, Giuseppe Banfi, Remo Guerrini, Paola Secchiero, Stefano Volinia, Francesca Granucci, Eva Reali
• Journal: European journal of immunology (Eur J Immunol) Vol. 53 Issue 4 Pg. e2149702 (04 2023) ISSN: 1521-4141 [Electronic] Germany
• PMID: 36722608 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.

Chemical References

• Imiquimod
• Receptors, Antigen, T-Cell
• CCR4 protein, human
• Receptors, CCR4

Topics

• Humans
• Mice
• Animals
• Arthritis, Psoriatic
• CD8-Positive T-Lymphocytes
• Imiquimod
• Mice, Inbred C57BL
• Psoriasis
• Skin Diseases
• Inflammation
• Receptors, Antigen, T-Cell (genetics)
• Receptors, CCR4