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J Clin Invest. 2018 Oct 1;128(10):4727-4741. doi: 10.1172/JCI99308. Epub 2018 Sep 17.

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

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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.


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.


Autoimmune diseases; Autoimmunity; Demyelinating disorders; Extracellular matrix; Neuroscience

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