6533b7d0fe1ef96bd125ae98
RESEARCH PRODUCT
Pro-inflammatory T helper 17 directly harms oligodendrocytes in neuroinflammation.
Stefan BittnerHélène JamannQiao-ling CuiJulian T. LöffelFrauke ZippMiriam SchillnerBeatrice WasserJack P. AntelJérôme BirkenstockOlivier TastetCatherine LarochelleCatherine LarochelleDirk LuchtmanAlbrecht Strohsubject
Programmed cell deathEncephalomyelitis Autoimmune ExperimentalCentral nervous systemFreund's AdjuvantoligodendrocytesMice Transgenicglutamate03 medical and health sciencesMyelinMice0302 clinical medicineImmunology and Inflammationintravital microscopymedicineAnimalsNeuroinflammation030304 developmental biologyInflammationMice Knockout0303 health sciencesMultidisciplinaryChemistryMultiple sclerosisGlutamate receptorMembrane ProteinsCD29Biological SciencesCD29 blockademedicine.disease420Oligodendrocyte3. Good healthCell biologyDNA-Binding ProteinsMice Inbred C57BLOligodendrogliamedicine.anatomical_structurePertussis ToxinTh17 CellsMyelin-Oligodendrocyte Glycoprotein030217 neurology & neurosurgerydescription
Significance Multiple sclerosis (MS) is a neuroinflammatory, demyelinating disease that represents one of the most frequent causes of irreversible disability in young adults. Treatment options to halt disability are limited. We discovered that T helper (Th)17 cells in contact with oligodendrocytes produce higher levels of glutamate and induce significantly greater oligodendrocyte damage than their Th2 counterpart. Blockade of CD29, which is linked to glutamate release pathways and expressed in high levels on Th17 cells, preserved human oligodendrocyte processes from Th17-mediated injury. Our data thus provide evidence for the direct and deleterious attack of Th17 cells on the myelin compartment and show the potential for therapeutic opportunities to protect oligodendrocytes’ myelinating processes in MS.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-08-20 | Proceedings of the National Academy of Sciences of the United States of America |