PuSH - Publikationsserver des Helmholtz Zentrums München

Pilz, A.C. ; Briem, E.* ; Colli, M.* ; Hillig, C.* ; Lavazais, S.* ; Menden, M.P. ; Biedermann, T.* ; Lauffer, F.* ; Eyerich, K.* ; De Vos, S.* ; Jargosch, M.

Inhibition of salt-inducible kinases 2 and 3 reduces inflammatory signature in psoriasis.

J. Invest. Dermatol., DOI: 10.1016/j.jid.2026.07.033 (2026)
Verlagsversion DOI
Open Access Hybrid
Creative Commons Lizenzvertrag
Psoriasis is a highly prevalent inflammatory skin disease for which good systemic therapeutic agents are available. However, there is still a great need for new treatment options, especially oral ones. Salt-inducible kinases (SIKs) are emerging as new druggable targets in immune diseases, and the SIK2/SIK3 inhibitor GLPG3970 recently proved to efficiently reduce psoriasis lesions in a phase Ib trial. This study assesses the molecular events underlying the beneficial effects of SIK2/SIK3 inhibition through GLPG3970 in psoriasis. Using spatial transcriptomics and single-cell sequencing, abundant expression of SIK2 and SIK3 but not of SIK1 was observed in psoriatic skin. In vitro, GLPG3970 reduced psoriasis marker cytokines and chemokines (TNF, IFNγ, IL-1β, IL-6, CXCL8, CXCL10) in peripheral mononuclear cells, T cells, and fibroblasts but not in keratinocytes. Bulk RNA sequencing of lesional psoriasis biopsies treated ex vivo with GLPG3970 and of biopsies received from responders versus placebo-treated patients from the clinical trial showed downregulation of inflammatory pathways with suppression of IL1B , CXCL1 , CXCL8 , CEBPB , CD177 , and CLEC5A in both settings. In summary, this study suggests that specific inhibition of SIK2/SIK3 reduces acute-phase immunity and neutrophil recruitment in psoriasis.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Acute Inflammation ; Dendritic Cells ; Macrophages ; Monocytes ; Neutrophils
ISSN (print) / ISBN 0022-202X
e-ISSN 1523-1747
Zeitschrift Journal of Investigative Dermatology, The
Verlag Elsevier
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Allergy Research (IAF)
Institute of Computational Biology (ICB)