P81 Study on the role of SLC7A11-mediated amino acid metabolism dysregulation in the pathogenesis of psoriasis
Year: 2024
Type: conference-abstract
Abstract: Psoriasis is an inflammatory skin disease characterized by an abnormally activated immune response and excessive keratinocyte proliferation. Although metabolic disorders have been observed in psoriasis, the role of amino acid transporters in keratinocytes remains unclear. This study aimed to investigate the role and mechanism of the cystine/glutamate antiporter (SLC7A11) in psoriasis. To achieve this, we generated Cre and CreERT mice to specifically knock out the SLC7A11 gene in K14-expressing cells. We used the imiquimod (IMQ) model to induce skin inflammation and tested the effect of the SLC7A11 inhibitor, imidazole ketone erastin. Additionally, we analysed the resulting proteomic and metabolomic changes in SLC7A11 knockdown keratinocytes. Our findings revealed that SLC7A11 expression was increased in the keratinocytes of psoriatic lesions in both humans and mice. Deletion of SLC7A11 in keratinocytes reduced their proliferation and the inflammatory response induced by IMQ. SLC7A11 deletion or inhibition blocked the expansion of neutrophils and macrophages and reduced the release of CXCL2, CXCL5 and CCL20 in the IMQ-induced model. Furthermore, knocking down SLC7A11 expression blocked DNA synthesis, disrupted the cell cycle, and impaired intracellular signalling. Concurrently, intracellular amino acid metabolism, particularly cysteine metabolism, underwent dramatic changes, leading to a reduced inflammatory response. SLC7A11-mediated amino acid uptake plays a crucial role in the pathogenesis of psoriasis by regulating keratinocyte proliferation and inflammatory responses. Targeting SLC7A11 could be a promising immunosuppressive strategy for controlling psoriatic inflammation. This study provides new insights into the metabolic aspects of psoriasis and highlights the potential of SLC7A11 as a therapeutic target.
Source: British Journal of Dermatology
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4405230697