Schwann cell-derived periostin promotes autoimmune peripheral polyneuropathy via macrophage recruitment
| Autor: | 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 |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Pathology Autoimmune diseases Chronic inflammatory demyelinating polyneuropathy Autoimmunity Mice SCID Neurodegenerative medicine.disease_cause Medical and Health Sciences Myelin Mice 0302 clinical medicine Autoimmune Process Mice Inbred NOD 2.1 Biological and endogenous factors Aetiology Chronic Inflammatory Demyelinating Mice Knockout CD11b Antigen Pain Research General Medicine Extracellular matrix medicine.anatomical_structure Neurological Sciatic nerve Chronic Pain Research Article medicine.medical_specialty Knockout Immunology Polyradiculoneuropathy Schwann cell Periostin SCID Autoimmune Disease Macrophage chemotaxis 03 medical and health sciences medicine Animals Humans Demyelinating disorders Peripheral Neuropathy business.industry Inflammatory and immune system Macrophages Neurosciences medicine.disease 030104 developmental biology Polyradiculoneuropathy Chronic Inflammatory Demyelinating Inbred NOD Schwann Cells business Cell Adhesion Molecules 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | The Journal of clinical investigation, vol 128, iss 10 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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