Upregulation of CD74 and its potential association with disease severity in subjects with ischemic stroke

Liu Yang, Ying Kong, Honglei Ren, Minshu Li, Chang Juan Wei, Elaine Shi, Wei Na Jin, Junwei Hao, Arthur Vandenbark, Halina Offner

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Macrophage migration inhibitory factor (MIF) is a key cytokine/chemokine in the activation and recruitment of inflammatory T lymphocytes known to exacerbate experimental stroke severity. MIF effects are mediated through its primary cellular receptor, CD74, the MHC class II invariant chain present on all class II expressing cells, including monocytes, macrophages and dendritic cells (DC). We demonstrated previously that partial MHC class II/peptide constructs (pMHC) can effectively treat mice with experimental stroke, in part through their ability to competitively inhibit MIF/CD74 interactions and downstream signaling. However, the role of MIF and CD74 in human ischemic stroke is not yet well established. To evaluate the therapeutic potential for pMHC, we assessed MIF and CD74 expression levels and their association with disease outcome in subjects with ischemic stroke. MIF levels were assessed in blood plasma by ELISA and CD74 expression was quantified by flow cytometry and qRT-PCR in peripheral blood mononuclear cells (PBMCs) obtained from subjects with ischemic stroke and age and sex-matched healthy controls (HC). MIF levels were increased in plasma and the number of CD74+ cells and CD74 mRNA expression levels were significantly increased in PBMC of subjects with ischemic stroke versus HC, mainly on CD4+ T cells, monocytes and DC. Greater increases of CD74+ cells were seen in subjects with cortical vs. subcortical infarcts and the number of CD74+ cells in blood correlated strongly with infarct size and neurological outcomes. However, differences in MIF and CD74 expression were not affected by age, gender or lesion laterality. Increased CD74 expression levels may serve as a useful biomarker for worse stroke severity and predicted outcomes in subjects with ischemic stroke and provide a rationale for potential future treatment with pMHC constructs.

Original languageEnglish (US)
JournalNeurochemistry International
DOIs
StateAccepted/In press - Sep 13 2016

Fingerprint

Up-Regulation
Stroke
Blood Cells
Dendritic Cells
Monocytes
Cell Count
Macrophage Migration-Inhibitory Factors
T-Lymphocytes
Chemokines
Flow Cytometry
Biomarkers
Enzyme-Linked Immunosorbent Assay
Macrophages
Cytokines
Polymerase Chain Reaction
Messenger RNA
Peptides
Therapeutics

Keywords

  • CD74
  • Inflammation
  • Macrophage Migration Inhibitory Factor
  • Partial MHC class II constructs
  • Stroke

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Upregulation of CD74 and its potential association with disease severity in subjects with ischemic stroke. / Yang, Liu; Kong, Ying; Ren, Honglei; Li, Minshu; Wei, Chang Juan; Shi, Elaine; Jin, Wei Na; Hao, Junwei; Vandenbark, Arthur; Offner, Halina.

In: Neurochemistry International, 13.09.2016.

Research output: Contribution to journalArticle

Yang, Liu ; Kong, Ying ; Ren, Honglei ; Li, Minshu ; Wei, Chang Juan ; Shi, Elaine ; Jin, Wei Na ; Hao, Junwei ; Vandenbark, Arthur ; Offner, Halina. / Upregulation of CD74 and its potential association with disease severity in subjects with ischemic stroke. In: Neurochemistry International. 2016.
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