Microrna-150 controls experimental autoimmune encephalomyelitis by regulating cd4 t cell differentiation and function
2020
Autori:
Piket, ElianeN'diaye, Marie
Ewing, Ewoud
Williams, L
Olofsson, Anna
Mrugalla, L
Zisiadis, Georgios Alkis
Lavrnja, Irena
Nyberg, William
Espinosa, Alexander
Kular, Lara
Cacais, André Ortlieb Guerreiro
Jagodić, Maja
Tip dokumenta:
Konferencijski prilog (Objavljena verzija)
,
© 2020, © SAGE Publications
Metapodaci
Prikaz svih podataka o dokumentuApstrakt:
Background: MicroRNAs are small non-coding RNA molecules
that have an important role in the fine tuning of all biological processes
and are often found to be dysregulated in diseases, such as
multiple sclerosis (MS). MS is an immune-mediated disease of
the central nervous system characterized by demyelination, axonal
loss and neurodegeneration. We have previously shown micro-
RNA-150 (miR-150) levels to be elevated in cell-free cerebrospinal
fluid (CSF) of MS patients compared to controls.
Objectives: The aim of this study is to further understand the
physiopathological function of miR-150 using experimental autoimmune
encephalomyelitis (EAE), a mouse model for MS.
Methods: To establish its role in-vivo, we generated miR-150
knock-out (KO) and knock-in (KI) mice using CRISPR/Cas9.
Immune profiling using flow cytometry as well as RNA sequencing
were used to understand underlying mechanisms.
Results: After induction of EAE, miR-150 KO mice showed ameliorated
disease compared to WT littermate controls while miR-150
KI mice presented with exacerbated disease. An ameliorated disease
in miR-150 KO was accompanied by a decreased infiltration
of CD4 T cells compared to WT and KI. At priming stage of EAE
we found that miR-150 KO had an increase in regulatory CD4 T
cells (TREGS). Furthermore, after reconstitution of T cell deficient
animals, CD4 T cells from miR-150 KO mice could protect against
EAE and also showed an increased FOXP3 expression. A role of
miR-150 in regulating TREG cells was further substantiated by transcriptome
profiling, where miR-150 KO CD4 T cells suggested an
enhancement of TREG phenotype as well as a diminished translation
in miR-150 KO CD4 T cells. Moreover, the results implicated miR-
150 with mechanisms such as translation, autophagy and metabolism
as well T cell proliferation and differentiation.
Conclusions: miR-150 deficiency ameliorated EAE and favored
a more anti-inflammatory environment while miR-150 expression
promoted pathogenic CD4 T cells subsets, potentially associated
with metabolic mechanisms.
U:
- 8th Joint ACTRIMS-ECTRIMS Meeting: MSVirtual 2020; 2020 Sep 11-13; Virtual Meeting. Sage Publications Ltd.; 2020. p. 583. (Multiple Sclerosis Journal; Vol. 26; No. 3 Suppl.).