Details

Autor(en) / Beteiligte

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

Titel

cAMP response element modulator α suppresses PD-1 expression and promotes effector CD4+ T cells in psoriasis

Ist Teil von

• The Journal of immunology (1950), 2021-06, Vol.207 (1), p.55-64

Erscheinungsjahr

2021

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 co-receptor 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. Here 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 where it trans -represses gene expression and co-recruits DNMT3a mediating DNA methylation. As keratinocytes limit inflammation by PD-1 ligand expression, and here 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 which can deserve clinical exploitation.