@article{e8a701622fb1483c99016fd2d5d5cb72,
title = "Schwann cell-derived periostin promotes autoimmune peripheral polyneuropathy via macrophage recruitment",
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.",
author = "Allard, {Denise E.} and Yan Wang and Li, {Jian Joel} and Bridget Conley and Xu, {Erin W.} and David Sailer and Caellaigh Kimpston and Rebecca Notini and Smith, {Collin Jamal} and Emel Koseoglu and Joshua Starmer and Zeng, {Xiaopei L.} and Howard, {James F.} and Ahmet Hoke and Scherer, {Steven S.} and Su, {Maureen A.}",
note = "Funding Information: Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke (RO1NS079683, MAS, principal investigator, and R01NS107851, MAS and SSS, principal investigators); the GBS/CIDP Foundation (MAS, principal investigator); a National Institute of Allergy and Infectious Diseases (NIAID) Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (T32 AI 007273; J.P. Ting, principal investigator); and a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Ruth L. Kirschstein NRSA Institutional Research Training Grant (T32 DK 007750; R.J. Falk, principal investigator). All flow cytometric experiments were carried out with the support of the UNC Flow Cytometry Core Facility. The UNC Flow Cytometry Core Facility is supported in part by a Cancer Center Core Support Grant (P30 CA016086, to the UNC Lineberger Comprehensive Cancer Center); in part by a North Carolina Biotech Center Institutional Support Grant (2012-IDG-1006); and by the Office of the Director of UNC-CH. Confocal and wide-field microscopy for murine samples was performed at the UNC Neuroscience Center Microscopy Core Facility, which is supported in part by funding from the National Institute of Neurological Disorders and Stroke (NINDS) (P30 NS045892) and a National Institute of Child Health and Human Development Intellectual and Developmental Disabilities Research Center Support Grant (U54 HD079124). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2018 American Society for Clinical Investigation. All rights reserved.",
year = "2018",
month = oct,
day = "1",
doi = "10.1172/JCI99308",
language = "English (US)",
volume = "128",
pages = "4727--4741",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "10",
}