# Autoimmune Mechanisms in Peripheral Neuropathy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $506,773

## Abstract

Abstract
Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is the most common acquired chronic
autoimmune neuropathy. Current treatments for CIDP are non-specific, ineffective in one-third of patients, and
do not result in complete remission in most patients. Thus, more effective, mechanism-based therapies are
needed, and understanding the immune tolerance defects that result in PNS autoimmunity will enable their
development. Studies to date suggest a model in which CD4+ T cells, macrophages, and complement lead to
the autoimmune destruction of Schwann cells in the PNS. Our data indicate that Schwann cells unexpectedly
undergo changes during autoimmune attack that may expand the inflammatory response. Schwann cells turn
on expression of Periostin, a secreted extracellular matrix protein important in chemotaxis of pathogenic
macrophages; increase expression of CD49b, an integrin important in binding complement protein C1q; and
induce expression of MHC Class II, a molecule required for antigen-presentation to CD4+ T cells. Thus, we
hypothesize that Schwann cell-associated changes may promote autoimmunity through increased macrophage
recruitment, complement deposition, and CD4+ T cell activation. To test this, we propose to determine
whether: i) Schwann cell-specific Periostin expression is sufficient to drive macrophage recruitment and
neuropathy development; ii) loss of CD49b in Schwann cells and/or C1q prevents complement activation and
protects from neuropathy; and iii) Schwann cell-specific MHCII deficiency dampens CD4+ T cell stimulation
and protects against PNS autoimmunity. These Aims will be tested in CIDP mouse models and patient nerve
biopsies. This project takes advantage of complementary expertise of the multiple PI's (Dr. Su in PNS
autoimmunity and Dr. Scherer in Schwann cell biology) to elucidate the role of Schwann cells in promoting
demyelinating neuropathy. Successful completion of the Aims of this project will pave the way to identifying
new targets for mechanism-based immunotherapeutic interventions for CIDP. Additionally, findings from these
studies will contribute to a broader understanding of how Schwann cells may amplify inflammation in immune-
mediated diseases of the PNS.

## Key facts

- **NIH application ID:** 9998044
- **Project number:** 5R01NS107851-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** STEVEN Simon Scherer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $506,773
- **Award type:** 5
- **Project period:** 2018-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998044

## Citation

> US National Institutes of Health, RePORTER application 9998044, Autoimmune Mechanisms in Peripheral Neuropathy (5R01NS107851-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9998044. Licensed CC0.

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