RT Journal Article
SR Electronic
T1 Cholesterol promotes <em>IFNG</em> mRNA expression in CD4<sup>+</sup> effector/memory cells by SGK1 activation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202402890
DO 10.26508/lsa.202402890
VO 7
IS 12
A1 Hanin, Aurélie
A1 Comi, Michela
A1 Sumida, Tomokazu S
A1 Hafler, David A
YR 2024
UL https://www.life-science-alliance.org/content/7/12/e202402890.abstract
AB IFNγ-secreting T cells are central for the maintenance of immune surveillance within the central nervous system (CNS). It was previously reported in healthy donors that the T-cell environment in the CNS induces distinct signatures related to cytotoxic capacity, CNS trafficking, tissue adaptation, and lipid homeostasis. These findings suggested that the CNS milieu consisting predominantly of lipids mediated the metabolic conditions leading to IFNγ-secreting brain CD4 T cells. Here, we demonstrate that the supplementation of CD4+CD45RO+CXCR3+ cells with cholesterol modulates their function and increases IFNG expression. The heightened IFNG expression was mediated by the activation of the serum/glucocorticoid-regulated kinase (SGK1). Inhibition of SGK1 by a specific enzymatic inhibitor significantly reduces the expression of IFNG. Our results confirm the crucial role of lipids in maintaining T-cell homeostasis and demonstrate a putative role of environmental factors to induce effector responses in CD4+ effector/memory cells. These findings offer potential avenues for further research targeting lipid pathways to modulate inflammatory conditions.The data are available from the corresponding author upon request.