Schwann cells promote spontaneous autoimmune peripheral polyneuropathy
Public Deposited- Last Modified
- March 19, 2019
- Creator
-
Allard Trout, Denise
- Affiliation: School of Medicine, Department of Microbiology and Immunology
- Abstract
- Chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barré syndrome (GBS) are autoimmune demyelinating diseases of the peripheral nervous system (PNS). During CIDP and GBS, the immune system attacks Schwann cells that compose the myelin sheath leading to impaired sensorimotor nerve function; however, Schwann cells are not merely passive bystanders in this autoimmune attack. We show here that Schwann cells actively promote disease pathogenesis in murine models of CIDP and GBS through upregulation of the extracellular matrix (ECM) protein periostin (Postn) and integrin (Itg)-α2 (CD49b). Firstly, increased Postn secretion by Schwann cells directly promoted macrophage chemotaxis into the PNS via interaction with ItgαV and ItgαM (CD11b). We also showed that although PNS-infiltrating macrophages expressed both pro- and anti-inflammatory markers, macrophages in the PNS are pathogenic effectors since their depletion resulted in delayed disease onset and reduced disease incidence. Secondly, we showed increased CD49b expression on Schwann cells rather than NK cells or NK T cells during neuropathy. CD49b associated with the complement protein C1q suggesting a possible immunological role for CD49b.
- Date of publication
- August 2018
- Keyword
- DOI
- Resource type
- Rights statement
- In Copyright
- Advisor
- Matsushima, Glenn
- Vilen, Barbara
- Miao, Edward
- Tisch, Roland
- Su, Maureen
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2018
- Language
Relations
- Parents:
This work has no parents.
Items
| Thumbnail | Title | Date Uploaded | Visibility | Actions |
|---|---|---|---|---|
|
|
AllardTrout_unc_0153D_18085.pdf | 2019-04-12 | Public | Download |