Cyclic AMP Response Element Modulator-α Suppresses PD-1 Expression and Promotes Effector CD4+ T Cells in Psoriasis

Sigrun R. Hofmann, Emil Carlsson, Franz Kapplusch, Ana L. Carvalho, Triantafillos Liloglou, Felix Schulze, Susanne Abraham, Sarah Northey, Susanne Russ, Anna E. A. Surace, Nobuya Yoshida, George C. Tsokos, Christian M. Hedrich

Research output: Contribution to journalArticle (journal)peer-review

Abstract

Effector CD4+ T lymphocytes contribute to inflammation and tissue damage in psoriasis, but the underlying molecular mechanisms remain poorly understood. The transcription factor CREMα controls effector T cell function in people with systemic autoimmune diseases. The inhibitory surface coreceptor PD-1 plays a key role in the control of effector T cell function and its therapeutic inhibition in patients with cancer can cause psoriasis. In this study, we show that CD4+ T cells from patients with psoriasis and psoriatic arthritis exhibit increased production of IL-17 but decreased expression of IL-2 and PD-1. In genetically modified mice and Jurkat T cells CREMα expression was linked to low PD-1 levels. We demonstrate that CREMα is recruited to the proximal promoter of PDCD1 in which it trans-represses gene expression and corecruits DNMT3a-mediating DNA methylation. As keratinocytes limit inflammation by PD-1 ligand expression and, in this study, reported reduced expression of PD-1 on CD4+ T cells is linked to low IL-2 and high IL-17A production, our studies reveal a molecular pathway in T cells from people with psoriasis that can deserve clinical exploitation.
Original languageEnglish
Pages (from-to)55-64
JournalThe Journal of Immunology
Volume207
Issue number1
DOIs
Publication statusPublished - 1 Jul 2021

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