Figure 9. Schematic illustration of GLS1-mediated glutaminolysis contributing to the pathogenesis of psoriasis.

In patients with psoriasis, consecutive activation of MALT1 protease stabilizes c-Jun, which binds to the GLS1 promoter region and increases expression of GLS1, thus leading to aberrant glutaminolysis. GLS1-mediated glutaminolysis augments intracellular acetyl-CoA via the TCA cycle, which contributes to histone H3 acetylation of the IL17A promoter and RORC transcriptional activity, thereby aggravating T17 cell differentiation in psoriasis. On the other hand, IL-17A/MALT1/c-Jun axis–induced GLS1-mediated glutaminolysis also enhances the proliferation of and chemokine secretion by keratinocytes, which increases the recruitment of activated T cells in skin lesions. Together, the effects of the aberrant MALT1/c-Jun/GLS1 pathway on CD4⁺ and γδ T cells, together with keratinocytes contribute to the formation of psoriatic skin lesions. KCs, keratinocytes.