Schwann cell‚Äìderived periostin promotes autoimmune peripheral polyneuropathy via macrophage recruitment
Authors: Denise E Allard
Caellaigh Kimpston
Jian Joel Li
Collin-Jamal Smith
Rebecca Notini
Yan Wang
Erin W Xu
David Sailer
Steven S Scherer
Bridget Conley
Xiaopei L Zeng
Joshua Starmer
Emel Koseoglu
Maureen A Su
Ahmet Hoke
James F Howard Jr
Journal: Journal of Clinical Investigation (2018)
Discipline: CLINICAL MEDICINE
Keywords: Autoimmune diseases; Autoimmunity; Demyelinating disorders; Extracellular matrix; Neuroscience.
Affiliations: Department of Microbiology and Immunology and., Department of Pediatrics, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, North Carolina, USA., Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, California, USA., Neurology Department, School of Medicine, Erciyes University, Kayseri, Turkey, Department of Genetics and 7Department of Neurology, UNC-CH, Chapel Hill, North Carolina, USA, Department of Neurology, UNC-CH, Chapel Hill, North Carolina, USA, Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA, Department of Pediatrics, UCLA, Los Angeles, California, USA.

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. 

Retracted: No

PubPeer comments:
 Current findings demonstrate the participation of Schwann cells in peripheral polyneuropathy by overexpression of the matricellular protein Periostin. Then the effect of deficiency and sufficiency of Periostin was looked into in the different genetic composition of neuroimmunopathic mice model. Despite another extracellular matrix protein, Thrombospondin was upregulated, the effect of Thrombospondin was overlooked in subsequent experiments. Whether any interaction exists between those two players also remained unclear. ,