title: Partial MHC class II constructs as novel immunomodulatory therapy for stroke.
abstract: The worldwide prevalence of stroke continues to rise despite recent successes in treating acute ischemic stroke. With limited patient eligibility and associated risk of tPA and mechanical thrombectomy, new preventive and therapeutic modalities are needed to stave the rising wave of stroke. Inflammation plays a key role in brain damage after cerebral ischemia, and novel therapies that target pro-inflammatory cells have demonstrated promise for treatment for stroke. Partial MHC class II constructs have been shown to prevent and/or reverse clinical signs of various inflammatory diseases such as experimental autoimmune encephalomyelitis, collagen-induced arthritis and experimental autoimmune uveitis, by reducing the number and frequency of activated cells in the damaged CNS. Herein, we review the use of partial MHC class II constructs as a novel treatment for ischemic stroke. These constructs have been shown to reduce infarct volume and neurological deficit in various cerebral ischemia models in young adult and aging male and female mice. In addition, partial MHC class II constructs were shown to reverse stroke-associated splenic atrophy and promote a protective M2 macrophage/microglia phenotype in the CNS which contributes to tissue repair and recovery after stroke. By addressing remaining STAIR criteria, such as efficacy in large animal models of stroke, these constructs will be prime candidates for clinical trials of acute ischemic stroke.
authors: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd, Portland, OR, 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
authors: Gil
authors: G
authors: Benedek
authors: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd, Portland, OR, 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA; Department of Molecular Microbiology & Immunology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
authors: Arthur A
authors: AA
authors: Vandenbark
authors: Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA.
authors: Nabil J
authors: NJ
authors: Alkayed
authors: Neuroimmunology Research, VA Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd, Portland, OR, 97239, USA; Department of Neurology, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA; Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR, 97239, USA. Electronic address: offnerva@ohsu.edu.
authors: Halina
authors: H
authors: Offner
mesh_terms: D000818:Animals; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000235:genetics / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D020521:Stroke / Q000235:genetics / Q000276:immunology* / Q000628:therapy*
keywords: Immunotherapy; Inflammation; Partial MHC class II construct; Recombinant T-cell receptor ligand; Stroke