CD4+CD25hiFoxP3+ regulatory T cells (Treg cells) are key controllers of immune self-tolerance, and their suppressive function is impaired in people with relapsing-remitting multiple sclerosis (pwRR-MS). Because the mechanisms underlying this condition are still ill-defined, we investigated the role of Treg cell-derived extracellular vesicles (Treg-EVs) in Treg cell dysfunction observed in pwRR-MS. We found that Treg-EVs from healthy individuals inhibit CD4+ conventional T (Tconv) cells by shuttling miR-142-3p from the Treg cell to the Tconv cell. There, miR-142-3p down-regulated mRNAs necessary for Tconv cell growth and effector functions, such as the redox controller cystine carrier SLC7A11. However, Treg cells from pwRR-MS released EVs containing reduced amounts of miR-142-3p, resulting in impaired suppressive function. Furthermore, Treg-EV miR-142-3p inversely correlated with the disability score and gadolinium-enhancing lesions in pwRR-MS. Together, our results elucidate a molecular mechanism involving miR-142-3p shuttled by Treg-EVs in the control of immune self-tolerance and unveil its pathogenetic implications in human autoimmunity.
MicroRNA-142-3p shuttling in extracellular vesicles marks regulatory T cell dysfunction in multiple sclerosis / De Rosa, G., Russo, C., Garavelli, S., Di Silvestre, D., Spatocco, I., Mele, G., Rocca, C.L., Colamatteo, A., Carbone, F., Fusco, C., Passaro, F., Carpi, D., Tagliabue, E., Prattichizzo, F., Brambilla, F., Mauri, P., Hoxha, M., Bollati, V., Giusti, I., Dolo, V., et al.. - In: SCIENCE TRANSLATIONAL MEDICINE. - ISSN 1946-6242. - 17:800(2025). [10.1126/scitranslmed.adl1698]
MicroRNA-142-3p shuttling in extracellular vesicles marks regulatory T cell dysfunction in multiple sclerosis
Salvetti M.;Matarese G.;
2025
Abstract
CD4+CD25hiFoxP3+ regulatory T cells (Treg cells) are key controllers of immune self-tolerance, and their suppressive function is impaired in people with relapsing-remitting multiple sclerosis (pwRR-MS). Because the mechanisms underlying this condition are still ill-defined, we investigated the role of Treg cell-derived extracellular vesicles (Treg-EVs) in Treg cell dysfunction observed in pwRR-MS. We found that Treg-EVs from healthy individuals inhibit CD4+ conventional T (Tconv) cells by shuttling miR-142-3p from the Treg cell to the Tconv cell. There, miR-142-3p down-regulated mRNAs necessary for Tconv cell growth and effector functions, such as the redox controller cystine carrier SLC7A11. However, Treg cells from pwRR-MS released EVs containing reduced amounts of miR-142-3p, resulting in impaired suppressive function. Furthermore, Treg-EV miR-142-3p inversely correlated with the disability score and gadolinium-enhancing lesions in pwRR-MS. Together, our results elucidate a molecular mechanism involving miR-142-3p shuttled by Treg-EVs in the control of immune self-tolerance and unveil its pathogenetic implications in human autoimmunity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
