Details

Autor(en) / Beteiligte

• Procaccini, Claudio
• Garavelli, Silvia
• Carbone, Fortunata
• Di Silvestre, Dario
• La Rocca, Claudia
• Greco, Dario
• Colamatteo, Alessandra
• Lepore, Maria Teresa
• Russo, Claudia
• De Rosa, Giusy
• Faicchia, Deriggio
• Prattichizzo, Francesco
• Grossi, Sarah
• Campomenosi, Paola
• Buttari, Fabio
• Mauri, Pierluigi
• Uccelli, Antonio
• Salvetti, Marco
• Brescia Morra, Vincenzo
• Vella, Danila
• Galgani, Mario
• Mottola, Maria
• Zuccarelli, Bruno
• Lanzillo, Roberta
• Maniscalco, Giorgia Teresa
• Centonze, Diego
• de Candia, Paola
• Matarese, Giuseppe

Titel

Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential

Ist Teil von

• Immunity (Cambridge, Mass.), 2021-07, Vol.54 (7), p.1543-1560.e6

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Human CD4+CD25hiFOXP3+ regulatory T (Treg) cells are key players in the control of immunological self-tolerance and homeostasis. Here, we report that signals of pseudo-starvation reversed human Treg cell in vitro anergy through an integrated transcriptional response, pertaining to proliferation, metabolism, and transmembrane solute carrier transport. At the molecular level, the Treg cell proliferative response was dependent on the induction of the cystine/glutamate antiporter solute carrier (SLC)7A11, whose expression was controlled by the nuclear factor erythroid 2-related factor 2 (NRF2). SLC7A11 induction in Treg cells was impaired in subjects with relapsing-remitting multiple sclerosis (RRMS), an autoimmune disorder associated with reduced Treg cell proliferative capacity. Treatment of RRMS subjects with dimethyl fumarate (DMF) rescued SLC7A11 induction and fully recovered Treg cell expansion. These results suggest a previously unrecognized mechanism that may account for the progressive loss of Treg cells in autoimmunity and unveil SLC7A11 as major target for the rescue of Treg cell proliferation. [Display omitted] •SLC7A11 controls Treg cell proliferation induced by signals of pseudo-starvation•SLC7A11 coordinates the antioxidant response in proliferating Treg cells•Growth-defective Treg cells from RRMS patients fail to induce SLC7A11•DMF therapy restores Treg cell proliferation, inducing SLC7A11 in RRMS patients Altered immunological self-tolerance in relapsing-remitting multiple sclerosis (RRMS) associates with a reduced regulatory T cell proliferation. Procaccini et al. show a key role for the amino acid transporter SLC7A11 in this process, as its induction is impaired in RRMS patients and can be restored by treatment with dimethyl fumarate.