Signals of pseudo-starvation unveil the amino acid transporter SLC7A11 as key determinant in the control of Treg cell proliferative potential
| Autor: | Maria Lepore, Dario Di Silvestre, Fabio Buttari, Claudia La Rocca, Antonio Uccelli, Paola de Candia, Giuseppe Matarese, Danila Vella, Alessandra Colamatteo, Giusy De Rosa, Pierluigi Mauri, Sarah Grossi, Claudia Russo, Roberta Lanzillo, Vincenzo Brescia Morra, Mario Galgani, Maria Mottola, Giorgia Teresa Maniscalco, Paola Campomenosi, Claudio Procaccini, Diego Centonze, Marco Salvetti, Silvia Garavelli, Deriggio Faicchia, Bruno Zuccarelli, Francesco Prattichizzo, Fortunata Carbone, Dario Greco |
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| Přispěvatelé: | Procaccini, C., Garavelli, S., Carbone, F., Di Silvestre, D., La Rocca, C., Greco, D., Colamatteo, A., Lepore, M. T., Russo, C., De Rosa, G., Faicchia, D., Prattichizzo, F., Grossi, S., Campomenosi, P., Buttari, F., Mauri, P., Uccelli, A., Salvetti, M., Brescia Morra, V., Vella, D., Galgani, M., Mottola, M., Zuccarelli, B., Lanzillo, R., Maniscalco, G. T., Centonze, D., de Candia, P., Matarese, G. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Antiporter T-Lymphocytes SLC7A11 Relapsing-Remitting medicine.disease_cause T-Lymphocytes Regulatory Autoimmunity 0302 clinical medicine Immunology and Allergy Homeostasis Cells Cultured Cultured dimethyl fumarate biology autoimmunity Glutamate receptor hemic and immune systems Regulatory Transmembrane protein Cell biology Infectious Diseases 030220 oncology & carcinogenesis multiple sclerosi Female Human leptin metabolism multiple sclerosis proliferation starvation Treg cells xCT Adult Amino Acid Transport System y+ Cell Proliferation Humans Immune Tolerance Multiple Sclerosis Relapsing-Remitting NF-E2-Related Factor 2 Multiple Sclerosis Cells Immunology chemical and pharmacologic phenomena Settore MED/26 03 medical and health sciences Homeostasi medicine Amino acid transporter Treg cell Solute carrier family 030104 developmental biology biology.protein |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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