학술논문
PKM2 promotes Th17 cell differentiation and autoimmune inflammation by fine-tuning STAT3 activation
Document Type
Article
Author
Damasceno, Luis Eduardo Alves; Prado, Douglas Silva; Veras, Flavio Protasio; Fonseca, Miriam M.; Toller-Kawahisa, Juliana E.; Rosa, Marcos Henrique; Públio, Gabriel Azevedo; Martins, Timna Varela; Ramalho, Fernando S.; Waisman, Ari; Cunha, Fernando Queiroz; Cunha, Thiago Mattar; Alves-Filho, José Carlos
Source
The Journal of Experimental Medicine; October 2020, Vol. 217 Issue: 10 pe20190613-e20190613, 1p
Subject
Language
ISSN
00221007; 15409538
Abstract
Th17 cell differentiation and pathogenicity depend on metabolic reprogramming inducing shifts toward glycolysis. Here, we show that the pyruvate kinase M2 (PKM2), a glycolytic enzyme required for cancer cell proliferation and tumor progression, is a key factor mediating Th17 cell differentiation and autoimmune inflammation. We found that PKM2 is highly expressed throughout the differentiation of Th17 cells in vitro and during experimental autoimmune encephalomyelitis (EAE) development. Strikingly, PKM2 is not required for the metabolic reprogramming and proliferative capacity of Th17 cells. However, T cell–specific PKM2 deletion impairs Th17 cell differentiation and ameliorates symptoms of EAE by decreasing Th17 cell–mediated inflammation and demyelination. Mechanistically, PKM2 translocates into the nucleus and interacts with STAT3, enhancing its activation and thereby increasing Th17 cell differentiation. Thus, PKM2 acts as a critical nonmetabolic regulator that fine-tunes Th17 cell differentiation and function in autoimmune-mediated inflammation.