Unknown

Dataset Information

0

CD28 Autonomous Signaling Up-Regulates C-Myc Expression and Promotes Glycolysis Enabling Inflammatory T Cell Responses in Multiple Sclerosis.


ABSTRACT: The immunopathogenesis of multiple sclerosis (MS) depend on the expansion of specific inflammatory T cell subsets, which are key effectors of tissue damage and demyelination. Emerging studies evidence that a reprogramming of T cell metabolism may occur in MS, thus the identification of stimulatory molecules and associated signaling pathways coordinating the metabolic processes that amplify T cell inflammation in MS is pivotal. Here, we characterized the involvement of the cluster of differentiation (CD)28 and associated signaling mediators in the modulation of the metabolic programs regulating pro-inflammatory T cell functions in relapsing-remitting MS (RRMS) patients. We show that CD28 up-regulates glycolysis independent of the T cell receptor (TCR) engagement by promoting the increase of c-myc and the glucose transporter, Glut1, in RRMS CD4+ T cells. The increase of glycolysis induced by CD28 was important for the expression of inflammatory cytokines related to T helper (Th)17 cells, as demonstrated by the strong inhibition exerted by impairing the glycolytic pathway. Finally, we identified the class 1A phosphatidylinositol 3-kinase (PI3K) as the critical signaling mediator of CD28 that regulates cell metabolism and amplify specific inflammatory T cell phenotypes in MS.

SUBMITTER: Kunkl M 

PROVIDER: S-EPMC6628233 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

CD28 Autonomous Signaling Up-Regulates C-Myc Expression and Promotes Glycolysis Enabling Inflammatory T Cell Responses in Multiple Sclerosis.

Kunkl Martina M   Sambucci Manolo M   Ruggieri Serena S   Amormino Carola C   Tortorella Carla C   Gasperini Claudio C   Battistini Luca L   Tuosto Loretta L  

Cells 20190611 6


The immunopathogenesis of multiple sclerosis (MS) depend on the expansion of specific inflammatory T cell subsets, which are key effectors of tissue damage and demyelination. Emerging studies evidence that a reprogramming of T cell metabolism may occur in MS, thus the identification of stimulatory molecules and associated signaling pathways coordinating the metabolic processes that amplify T cell inflammation in MS is pivotal. Here, we characterized the involvement of the cluster of differentiat  ...[more]

Similar Datasets

| S-EPMC8257047 | biostudies-literature
2021-07-14 | GSE164475 | GEO
| S-EPMC8188696 | biostudies-literature
| S-EPMC6412077 | biostudies-literature
| S-EPMC7455120 | biostudies-literature
| S-EPMC4602034 | biostudies-literature
| S-EPMC8369021 | biostudies-literature
| S-EPMC4202149 | biostudies-literature
| S-EPMC7062195 | biostudies-literature
| S-EPMC7571595 | biostudies-literature