RT Journal Article
T1 Ferritin heavy chain supports stability and function of the regulatory T cell lineage
A1 Wu, Qian
A1 Carlos, Ana Rita
A1 Braza, Faouzi
A1 Bergman, Marie Louise
A1 Kitoko, Jamil Z.
A1 Bastos Amador, Patricia
A1 Cuadrado, Eloy
A1 Martins, Rui
A1 Oliveira, Bruna Sabino
A1 Martins, Vera C.
A1 Scicluna, Brendon P.
A1 Landry, Jonathan J.M.
A1 Jung, Ferris E.
A1 Ademolue, Temitope W.
A1 Peitzsch, Mirko
A1 Almeida Santos, Jose
A1 Thompson, Jessica
A1 Cardoso, Silvia
A1 Ventura, Pedro
A1 Slot, Manon
A1 Rontogianni, Stamatia
A1 Ribeiro, Vanessa
A1 Domingues, Vital Da Silva
A1 Cabral, Inês A.
A1 Weis, Sebastian
A1 Groth, Marco
A1 Ameneiro Quiñoy, Cristina
A1 Fidalgo Pérez, Miguel Ángel
A1 Wang, Fudi
A1 Demengeot, Jocelyne
A1 Amsen, Derk
A1 Soares, Miguel P.
K1 Regulatory T Cells
K1 FOXP3
K1 Iron Metabolism
K1 Ferritin Heavy Chain
K1 Ten–eleven Translocation Enzymes
AB Regulatory T (TREG) cells develop via a program orchestrated by the transcription factor forkhead box protein P3 (FOXP3). Maintenance of the TREG cell lineage relies on sustained FOXP3 transcription via a mechanism involving demethylation of cytosine-phosphate-guanine (CpG)-rich elements at conserved non-coding sequences (CNS) in the FOXP3 locus. This cytosine demethylation is catalyzed by the ten–eleven translocation (TET) family of dioxygenases, and it involves a redox reaction that uses iron (Fe) as an essential cofactor. Here, we establish that human and mouse TREG cells express Fe-regulatory genes, including that encoding ferritin heavy chain (FTH), at relatively high levels compared to conventional T helper cells. We show that FTH expression in TREG cells is essential for immune homeostasis. Mechanistically, FTH supports TET-catalyzed demethylation of CpG-rich sequences CNS1 and 2 in the FOXP3 locus, thereby promoting FOXP3 transcription and TREG cell stability. This process, which is essential for TREG lineage stability and function, limits the severity of autoimmune neuroinflammation and infectious diseases, and favors tumor progression. These findings suggest that the regulation of intracellular iron by FTH is a stable property of TREG cells that supports immune homeostasis and limits the pathological outcomes of immune-mediated inflammation
PB Nature Publishing Group
YR 2024
FD 2024-03-18
LK https://hdl.handle.net/10347/38616
UL https://hdl.handle.net/10347/38616
LA eng
NO Wu, Q., Carlos, A. R., Braza, F., Bergman, M., Kitoko, J. Z., Bastos-Amador, P., . . . Soares, M. P. (2024). Ferritin heavy chain supports stability and function of the regulatory T cell lineage. The EMBO Journal, 43(8), 1445–1483; 1483. doi:10.1038/s44318-024-00064-x
DS Minerva
RD 24 abr 2026