Dysregulated lipid metabolism networks modulate T-cell function in people with relapsing-remitting multiple sclerosis

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F24%3A10482657" target="_blank" >RIV/00216208:11110/24:10482657 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/24:10482657

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FftbWfoKfs" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=FftbWfoKfs</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/cei/uxae032" target="_blank" >10.1093/cei/uxae032</a>

Result language

angličtina

Original language name

Dysregulated lipid metabolism networks modulate T-cell function in people with relapsing-remitting multiple sclerosis

Original language description

Altered cholesterol, oxysterol, sphingolipid, and fatty acid concentrations are reported in blood, cerebrospinal fluid, and brain tissue of people with relapsing-remitting multiple sclerosis (RRMS) and are linked to disease progression and treatment responses. CD4 + T cells are pathogenic in RRMS, and defective T-cell function could be mediated in part by liver X receptors (LXRs)-nuclear receptors that regulate lipid homeostasis and immunity. RNA-sequencing and pathway analysis identified that genes within the &apos;lipid metabolism&apos; and &apos;signalling of nuclear receptors&apos; pathways were dysregulated in CD4 + T cells isolated from RRMS patients compared with healthy donors. While LXRB and genes associated with cholesterol metabolism were upregulated, other T-cell LXR-target genes, including genes involved in cellular lipid uptake (inducible degrader of the LDL receptor, IDOL), and the rate-limiting enzyme for glycosphingolipid biosynthesis (UDP-glucosylceramide synthase, UGCG) were downregulated in T cells from patients with RRMS compared to healthy donors. Correspondingly, plasma membrane glycosphingolipids were reduced, and cholesterol levels increased in RRMS CD4 + T cells, an effect partially recapitulated in healthy T cells by in vitro culture with T-cell receptor stimulation in the presence of serum from RRMS patients. Notably, stimulation with LXR-agonist GW3965 normalized membrane cholesterol levels, and reduced proliferation and IL17 cytokine production in RRMS CD4 + T-cells. Thus, LXR-mediated lipid metabolism pathways were dysregulated in T cells from patients with RRMS and could contribute to RRMS pathogenesis. Therapies that modify lipid metabolism could help restore immune cell function.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Clinical and Experimental Immunology

ISSN

0009-9104

e-ISSN

1365-2249

Volume of the periodical

217

Issue of the periodical within the volume

2

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

204-218

UT code for WoS article

001225339700001

EID of the result in the Scopus database

2-s2.0-85198684413