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

Collapse authors list.
Hofmann, Sigrun R, Carlsson, Emil, Kapplusch, Franz, Carvalho, Ana L, Liloglou, Triantafillos ORCID: 0000-0003-0460-1404, Schulze, Felix, Abraham, Susanne, Northey, Sarah, Russ, Susanne, Surace, Anna EA et al (show 3 more authors) (2021) Cyclic AMP Response Element Modulator-α Suppresses PD-1 Expression and Promotes Effector CD4+ T Cells in Psoriasis. JOURNAL OF IMMUNOLOGY, 207 (1). pp. 55-64.

Access the full-text of this item by clicking on the Open Access link.

Official URL: http://dx.doi.org/10.4049/jimmunol.2100240

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.

Item Type:	Article
Uncontrolled Keywords:	CD4-Positive T-Lymphocytes, Animals, Mice, Inbred C57BL, Humans, Mice, Arthritis, Psoriatic, Cyclic AMP Response Element Modulator, Programmed Cell Death 1 Receptor
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	05 May 2022 14:04
Last Modified:	17 Oct 2023 20:22
DOI:	10.4049/jimmunol.2100240
Open Access URL:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC86743...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3149562