Research, here’s the protein that blocks multiple sclerosis

NAPLES – A study recently demonstrated the key role of the cystine / glutamate-carrying amino acid channel in the function of regulatory T cells (Tregs) that block inflammation. Alterations in this transport pathway underlie the reduced growth of these cells in multiple sclerosis (MS). The study funded mainly by the Italian Multiple Sclerosis Foundation (FISM), the Ministry of University and Research (MUR) and the Ministry of Health, was published in the scientific journal Immunity (Cell Press). The research was coordinated by Professor Giuseppe Matarese of the Department of Molecular Medicine and Medical Biotechnology of the University of Naples Federico II, together with Dr. Paola de Candia of the IRCCS MultiMedica of Milan and Dr. Claudio Procaccini of the Institute for Endocrinology and the Experimental Oncology of the National Research Council (IEOS-CNR) of Naples. The research team has shown that the growth and function of regulatory T cells (Tregs), the cells that act as sentinels to maintain ‘immune tolerance’ and block inflammation, depend on the ability to produce a protein, called SLC7A11, a “transport channel” on the Treg membrane that allows the entry of the amino acid cystine and the exit of glutamate. The transport of this amino acid in the Tregs regulates the balance of free radicals, which are harmful to the function and growth of these same cells. Researchers have shown that Treg cells in multiple sclerosis (MS) patients have lost the ability to produce sufficient quantities of SLC7A11 and thus to defend themselves against excess free radicals, resulting in their inability to grow and maintain ‘immunological tolerance’. against myelin in the central nervous system, a condition typical of MS. The study also suggested that the production of SLC7A11 can be enhanced by conditions of reduced caloric intake (caloric restriction), capable of reducing the “metabolic overwork” of the cell present in conditions of overweight and obesity, which are associated with a worst course of MS. Finally, the research has shown that the Treg cells of MS patients can recover the ability to produce SCL7A11 after therapy with a first-line drug for MS, the “dimethyl fumarate – DMF”, which would consequently also allow the restoration of their ability to grow.

“Nobody knows why or for what metabolic defect the Tregs lose their ability to grow and their function in MS “- explains the coordinator of the study Prof. Giuseppe Matarese – but” The DMF would seem to mediate a “mimetic” action of a state of “caloric restriction (RC)” (defined as pseudo -starvation), and therefore these results would have therapeutic consequences, identifying SLC7A11 as a potential new target for a more targeted “immunometabolic” therapy for MS. “These implications are actually already being examined in a larger FISM-funded clinical study that aims to evaluate the anti-inflammatory effects of a therapeutic approach to MS by associating calorie restriction with classic first-line therapies, to evaluate the ability of the diet to enhance the therapeutic efficacy of MS drugs. The work involves, among others, neurologists such as professor Diego Centonze of the University of Rome Tor Vergata and of the IRCCS – Neuromed, professor Marco Salvetti of the University Sapienza University of Rome, professor Antonio Uccelli of the IRCCS Policlinico San Martino in Genoa, professors Vincenzo Brescia Morra and Roberta Lanzillo of the University of Naples Federico II, and doctor Giorgia Maniscalco of the AORN Cardarelli of Naples. In addition, Dr. Dario Di Silvestre and Dr. Pierluigi Mauri of the Institute of Biomedical Technologies of the CNR of Milan (ITB-CNR), Dr. Silvia Garavelli of the IEOS-CNR, and Dr. Fortunata Carbone and Claudia Russo also collaborated in the study. of the IRCCS – Santa Lucia Foundation of Rome / IEOS-CNR. Finally, it should be emphasized that the research is the result of an extensive network of collaborations also of other national research bodies (the University of Insubria in Varese, the Ri.MED Foundation in Palermo and AORN “Dei Colli” in Naples) and international (University of Tampere and the University of Helsinki, Finland).