Schwann cell-derived periostin promotes autoimmune peripheral polyneuropathy via macrophage recruitment

The Journal of Clinical Investigation
Denise E AllardMaureen A Su

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barre syndrome (GBS) are inflammatory neuropathies that affect humans and are characterized by peripheral nerve myelin destruction and macrophage-containing immune infiltrates. In contrast to the traditional view that the peripheral nerve is simply the target of autoimmunity, we report here that peripheral nerve Schwann cells exacerbate the autoimmune process through extracellular matrix (ECM) protein induction. In a spontaneous autoimmune peripheral polyneuropathy (SAPP) mouse model of inflammatory neuropathy and CIDP nerve biopsies, the ECM protein periostin (POSTN) was upregulated in affected sciatic nerves and was primarily expressed by Schwann cells. Postn deficiency delayed the onset and reduced the extent of neuropathy, as well as decreased the number of macrophages infiltrating the sciatic nerve. In an in vitro assay, POSTN promoted macrophage chemotaxis in an integrin-AM (ITGAM) and ITGAV-dependent manner. The PNS-infiltrating macrophages in SAPP-affected nerves were pathogenic, since depletion of macrophages protected against the development of neuropathy. Our findings show that Schwann cells promote macrophage infiltration by upregulating Postn and...Continue Reading

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Citations

Nov 5, 2019·Cancer Immunology, Immunotherapy : CII·Sophia H ZhangYuri L Bunimovich
Aug 8, 2020·The Journal of Veterinary Medical Science·Yuna ChoiJeongtae Kim
Mar 24, 2021·Journal of Neuroinflammation·Kathleen M Hagen, Shalina S Ousman
Jun 4, 2021·Nature Communications·Gustavo Della-Flora NunesM Laura Feltri

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Methods Mentioned

BETA
biopsy
reverse transcription PCR
biopsies
electron microscopy
light microscopy
flow cytometry
FACS
PCR

Software Mentioned

Leica Application Suite
R
FlowJo
JAX
QuantStudio
Leica DMR
Adobe Photoshop
Fiji

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