Faculty Collaboration Database

Targeting transmembrane-domain-less MOG expression to platelets prevents disease development in experimental autoimmune encephalomyelitis. Front Immunol 2022;13:1029356

Date

11/18/2022

Pubmed ID

36389708

Pubmed Central ID

PMC9647046

DOI

10.3389/fimmu.2022.1029356

Scopus ID

2-s2.0-85141698554 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system with no cure yet. Here, we report genetic engineering of hematopoietic stem cells (HSCs) to express myelin oligodendrocyte glycoprotein (MOG), specifically in platelets, as a means of intervention to induce immune tolerance in experimental autoimmune encephalomyelitis (EAE), the mouse model of MS. The platelet-specific αIIb promoter was used to drive either a full-length or truncated MOG expression cassette. Platelet-MOG expression was introduced by lentivirus transduction of HSCs followed by transplantation. MOG protein was detected on the cell surface of platelets only in full-length MOG-transduced recipients, but MOG was detected in transmembrane-domain-less MOG_1-157-transduced platelets intracellularly. We found that targeting MOG expression to platelets could prevent EAE development and attenuate disease severity, including the loss of bladder control in transduced recipients. Elimination of the transmembrane domains of MOG significantly enhanced the clinical efficacy in preventing the onset and development of the disease and induced CD4⁺Foxp3⁺ Treg cells in the EAE model. Together, our data demonstrated that targeting transmembrane domain-deleted MOG expression to platelets is an effective strategy to induce immune tolerance in EAE, which could be a promising approach for the treatment of patients with MS autoimmune disease.

Author List

Cai Y, Schroeder JA, Jing W, Gurski C, Williams CB, Wang S, Dittel BN, Shi Q

Authors

Qizhen Shi MD, PhD Professor in the Pediatrics department at Medical College of Wisconsin
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Central Nervous System
Encephalomyelitis, Autoimmune, Experimental
Immune Tolerance
Mice
Multiple Sclerosis
Myelin-Oligodendrocyte Glycoprotein