期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 322, 期 4, 页码 C699-C711出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00376.2021
关键词
experimental autoimmune encephalitis; nephronectin; ROS; Th17; Treg
资金
- JSPS KAKENHI [16K08221, 19K07492]
- Japan Rheumatism Foundation
- Grants-in-Aid for Scientific Research [19K07492, 16K08221] Funding Source: KAKEN
Blood levels of nephronectin (Npnt), a protein critical for kidney development, are elevated in EAE mice. Treatment with anti-Npnt antibody inhibits EAE development. The interaction between Npnt and SeP regulates the Th17/Treg balance via the ROS level.
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 oc881 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.
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