Kao, Yu-San and Mamareli, Panagiota and Dhillon-LaBrooy, Ayesha and Stueve, Philipp and Godoy, Gloria Janet and Velasquez, Lis Noelia and Raker, Verena Katharina and Weidenthaler-Barth, Beate and Boukhallouk, Fatima and Rampoldi, Francesca and Berod, Luciana and Sparwasser, Tim (2023) Targeting ACC1 in T cells ameliorates psoriatic skin inflammation. JOURNAL OF MOLECULAR MEDICINE-JMM, 101 (9). pp. 1153-1166. ISSN 0946-2716, 1432-1440
Full text not available from this repository. (Request a copy)Abstract
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 T helper (Th) and cytotoxic T (Tc) cells, and is associated with dysfunctional regulatory T cells (Tregs). Acetyl-CoA carboxylase 1 (ACC1), a rate-limiting enzyme of fatty acid synthesis (FAS), directs cell fate decisions between Th17 and Tregs and thus could be a promising therapeutic target for psoriasis treatment. Here, we demonstrate that targeting ACC1 in T cells by genetic ablation ameliorates skin inflammation in an experimental model of psoriasis by limiting Th17, Tc17, Th1, and Tc1 cells in skin lesions and increasing the frequency of effector Tregs in skin-draining lymph nodes (LNs).Key messagesACC1 deficiency in T cells ameliorates psoriatic skin inflammation in mice.ACC1 deficiency in T cells reduces IL-17A-producing Th17/Tc17/dysfunctional Treg populations in psoriatic lesions.ACC1 deficiency in T cells restrains IFN-& gamma;-producing Th1/Tc1 populations in psoriatic skin lesions and skin-draining LNs.ACC1 deficiency promotes activated CD44+CD25+ Tregs and effector CD62L-CD44+ Tregs under homeostasis and psoriatic conditions.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | REGULATORY T; FOXP3; DIFFERENTIATION; METABOLISM; RECEPTOR; KINASE; IL-2; ACC1; Psoriasis; Regulatory T cells (Tregs); Skin inflammation; Fatty acid synthesis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Mar 2024 14:19 |
| Last Modified: | 16 Mar 2024 14:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60223 |
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