Targeting ACC1 in T cells ameliorates psoriatic skin inflammation

• DOI: 10.1007/s00109-023-02349-w
• Publication Date: 2023-08-18T07:02:49Z
• Authors: Yu-San Kao; Panagiota Mamareli; Ayesha Dhillon-La...; Philipp Stüve; Gloria Janet Godoy; Lis Noelia Velasquez; Verena Katharina ...; Beate Weidenthale...; Fatima Boukhallouk; Francesca Rampoldi; Luciana Berod; Tim Sparwasser
• Keywords: Inflammation; 570; ddc:610; 610 Medizin; 610; 3. Good health; Mice; 610 Medical sciences; Animals; Psoriasis; Original Article; Skin; T-Lymphocytes, Cytotoxic; Acetyl-CoA Carboxylase

Psoriasis is a chronic inflammatory skin disease driven by the IL-23/IL-17 axis. It results from excessive activation of effector T cells, including helper (Th) and cytotoxic (Tc) associated with dysfunctional regulatory cells (Tregs). Acetyl-CoA carboxylase 1 (ACC1), rate-limiting enzyme fatty acid synthesis (FAS), directs cell fate decisions between Th17 Tregs thus could be promising therapeutic target for psoriasis treatment. Here, we demonstrate that targeting ACC1 in genetic ablation ameliorates inflammation an experimental model limiting Th17, Tc17, Th1, Tc1 lesions increasing frequency skin-draining lymph nodes (LNs). KEY MESSAGES : deficiency psoriatic mice. reduces IL-17A-producing Th17/Tc17/dysfunctional Treg populations lesions. restrains IFN-γ-producing Th1/Tc1 LNs. promotes activated CD44+CD25+ CD62L-CD44+ under homeostasis conditions.