GSH; a new link between Trained Immunity and immune regulation?

Human regulatory T cells (Tregs) are key players in the control of immunological homeostasis. In a publication in Immunity this month, Matarese et al. show that the amino acid transporter responsible for the generation of GSH (SLC7A11) is crucial in the regulation of proliferation of Tregs and subsequently contributes to the pathogenesis of patients with relapse-remitting multiple sclerosis (RRMS)

GSH has been linked to trained immunity before, so could this finding help us understand the link between trained immunity and immune regulation?

Tregs and immune homeostasis

Tregs preserve immunological self-tolerance by controlling the response of conventional Tcells. How they do this, is still under investigation but of high interest, since the number and function of Tregs is associated with many human auto-immune diseases, such as multiple sclerosis (MS).

In this publication, Matarese et al (members of the INTRIM consortium) describe how an unbiased approach led to the discovery of the cystine-glutamate antiporter SLC7A11 as key determinant involved in protection from oxidative stress and the control of Treg cell proliferation in both normal and pathological conditions, such as MS. Furthermore, they describe the pharmacological response of RRMS patients to the treatment with dimethyl fumarate (DMF).

The graphical abstract is depicted below and the full article can be found here.