Nephronectin influences EAE development by regulating the Th17/Treg balance via reactive oxygen species.
Machiko HondaTatsuya SegawaKiyoshi IshikawaMasahiro MaedaYoshiro SaitoShigeyuki KonPublished in: American journal of physiology. Cell physiology (2022)
Blood levels of the extracellular matrix protein nephronectin (Npnt), a protein critical for kidney development, are elevated in autoimmune experimental autoimmune encephalitis (EAE) mice, which are a model for multiple sclerosis. We found here that treatment with anti-Npnt antibody directed against the α 8 β 1 integrin-binding site (Npnt-blocking antibody) inhibits EAE development. The selenium transporter selenoprotein P (SeP) was identified as a novel Npnt-binding partner. In EAE, Npnt induced SeP and glutathione peroxidase 1 (GPx1) expression, followed by reactive oxygen species (ROS) inhibition in CD4 + T cells; these changes were disturbed by Npnt-blocking antibody treatment, which also caused suppressed differentiation of interleukin (IL)-17-producing CD4 + T-helper cells (Th17s) and elevated differentiation of regulatory T cells (Tregs). Treatment of EAE mice with the ROS scavenger N -acetyl cysteine (NAC) blocked the Npnt-blocking antibody-induced decrease in Th17 differentiation and increase in Treg differentiation. In conclusion, the interaction between Npnt and SeP contributes to EAE development by regulating the Th17/Treg balance via the ROS level.
Keyphrases
- reactive oxygen species
- regulatory t cells
- multiple sclerosis
- extracellular matrix
- cell death
- dendritic cells
- dna damage
- oxidative stress
- binding protein
- induced apoptosis
- poor prognosis
- metabolic syndrome
- transcription factor
- combination therapy
- protein protein
- small molecule
- insulin resistance
- replacement therapy
- signaling pathway
- dna binding
- smoking cessation