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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Immunol 2015 ; 16 (11): 1174-84 Nephropedia Template TP
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Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants #MMPMID26414764
De Rosa V; Galgani M; Porcellini A; Colamatteo A; Santopaolo M; Zuchegna C; Romano A; De Simone S; Procaccini C; La Rocca C; Carrieri PB; Maniscalco GT; Salvetti M; Buscarinu MC; Franzese A; Mozzillo E; La Cava A; Matarese G
Nat Immunol 2015[Nov]; 16 (11): 1174-84 PMID26414764show ga
Human regulatory T cells (Treg cells) that develop from conventional T cells (Tconv cells) following suboptimal stimulation via the T cell antigen receptor (TCR) (induced Treg cells (iTreg cells)) express the transcription factor Foxp3, are suppressive, and display an active proliferative and metabolic state. Here we found that the induction and suppressive function of iTreg cells tightly depended on glycolysis, which controlled Foxp3 splicing variants containing exon 2 (Foxp3-E2) through the glycolytic enzyme enolase-1. The Foxp3-E2?related suppressive activity of iTreg cells was altered in human autoimmune diseases, including multiple sclerosis and type 1 diabetes, and was associated with impaired glycolysis and signaling via interleukin 2. This link between glycolysis and Foxp3-E2 variants via enolase-1 shows a previously unknown mechanism for controlling the induction and function of Treg cells in health and in autoimmunity.