Cell reports · 2022
Pyruvate kinase M2 mediates IL-17 signaling in keratinocytes driving psoriatic skin inflammation.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Veras Flávio P, Publio Gabriel A, Melo Bruno M, Prado Douglas S, Norbiato Thainá, Cecilio Nerry T, Hiroki Carlos, Damasceno Luis Eduardo A, Jung Rebecca, Toller-Kawahisa Juliana E, Martins Timna V, Assunção Stella F, Lima Diogenes, Alves Marcia G, Vieira Gabriel V, Tavares Lucas A, Alves-Rezende Ana L R, Karbach Susanne H, Nakaya Helder I, Cunha Thiago M, Souza Cacilda S, Cunha Fernando Q, Sales Katiuchia U, Waisman Ari, Alves-Filho José C
Аннотация
Psoriasis is an inflammatory skin disease characterized by keratinocyte proliferation and inflammatory cell infiltration induced by IL-17. However, the molecular mechanism through which IL-17 signaling in keratinocytes triggers skin inflammation remains not fully understood. Pyruvate kinase M2 (PKM2), a glycolytic enzyme, has been shown to have non-metabolic functions. Here, we report that PKM2 mediates IL-17A signaling in keratinocytes triggering skin psoriatic inflammation. We find high expression of PKM2 in the epidermis of psoriatic patients and mice undergoing psoriasis models. Specific depletion of PKM2 in keratinocytes attenuates the development of experimental psoriasis by reducing the production of pro-inflammatory mediators. Mechanistically, PKM2 forms a complex with Act1 and TRAF6 regulating NF-κB transcriptional signaling downstream of the IL-17 receptor. As IL-17 also induces PKM2 expression in keratinocytes, our findings reveal a sustained signaling circuit critical for the psoriasis-driving effects of IL-17A, suggesting that PKM2 is a potential therapeutic target for psoriasis.