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

Authors :
Bridget Conley
Joshua Starmer
James F. Howard
Jian Joel Li
Xiaopei L. Zeng
Erin W. Xu
Caellaigh Kimpston
Yan Wang
Rebecca Notini
Ahmet Hoke
Emel Koseoglu
Maureen A. Su
Steven S. Scherer
Denise E. Allard
David Sailer
Collin Jamal Smith
Source :
The Journal of clinical investigation, vol 128, iss 10
Publication Year :
2018

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 suggest that POSTN is a novel target for the treatment of macrophage-associated inflammatory neuropathies.

Details

Language :
English
Database :
OpenAIRE
Journal :
The Journal of clinical investigation, vol 128, iss 10
Accession number :
edsair.doi.dedup.....c0b3121dc3a0a5d9c78dec9dfa98fafd