Inhibition of Mitochondrial Translation Ameliorates Imiquimod-Induced Psoriasis-Like Skin Inflammation by Targeting Vγ4+ γδ T Cells.
J Invest Dermatol
; 144(4): 844-854.e2, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-37832844
ABSTRACT
Psoriasis is an inflammatory skin disorder that is characterized by keratinocyte hyperproliferation in response to immune cell infiltration and cytokine secretion in the dermis. γδ T cells expressing the Vγ4 TCR chain are among the highest contributors of IL-17A, which is a major cytokine that drives a psoriasis flare, making Vγ4+ γδ T cells a suitable target to restrict psoriasis progression. In this study, we demonstrate that mitochondrial translation inhibition within Vγ4+ γδ T cells effectively reduced erythema, scaling, and skin thickening in a murine model of psoriatic disease. The antibiotic linezolid, which blocks mitochondrial translation, inhibited the production of mitochondrial-encoded protein cytochrome c oxidase in Vγ4+ γδ T cells and systemically reduced the frequencies of IL-17A+ Vγ4+ γδ T cells, effectively resolving IL-17A-dependent inflammation. Inhibiting mitochondrial translation could be a novel metabolic approach to interrupt IL-17A signaling in Vγ4+ T cells and reduce psoriasis-like skin pathophysiology.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Psoriasis
/
Dermatitis
Limits:
Animals
Language:
En
Journal:
J Invest Dermatol
Year:
2024
Document type:
Article
Affiliation country: