In vivo expression of recombinant pregnancy-specific glycoprotein 1a inhibits the symptoms of collagen-induced arthritis

Am J Reprod Immunol. 2014 Dec;72(6):527-33. doi: 10.1111/aji.12307. Epub 2014 Aug 12.

Abstract

Problem: The contribution of Pregnancy-specific glycoproteins (PSG), the major variant of PSG released into the circulation during pregnancy, to the pregnancy-dependent improvement of rheumatoid arthritis (RA) has still not been elucidated.

Method of study: Collagen-induced arthritis (CIA) was used to test the hypothesis that PSG1a when released into circulation has a modulatory role on the Th1-pathogenic response, thus improving the CIA symptoms. In vivo expression of PSG1a was induced by injection of the vaccinia (Vac)-based expression vector harboring the complete open-reading frame of PSG1a cDNA.

Results: In vivo PSG1a expression during the induction of CIA ameliorated the clinical symptoms, thereby reducing the arthritis score and incidence. Significantly lower levels of IL-17, IL-6, and IFN-γ, but higher levels of TGF-β and IL-10 were secreted by collagen type II-stimulated spleen mononuclear cells from Vac-PSG1a-treated mice compared with control mice. Moreover, Vac-PSG1a treatment promoted the increase in splenic CD4+CD25+Foxp3+ Treg cells.

Conclusion: Pre-clinical Vac-PSG1a treatment suppressed the Th1- and Th17-type-specific responses, leading to an increase in splenic Treg cells as well as IL-10- and TGF-β-secreting cells, with the CIA symptoms being ameliorated.

Keywords: Collagen induced arthritis; immunoregulation; pregnancy specific glycoproteins; regulatory T cells; rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / therapy*
  • CD4 Antigens / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Forkhead Transcription Factors / metabolism
  • Genetic Vectors / genetics
  • Humans
  • Immunomodulation*
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Male
  • Mice
  • Mice, Inbred DBA
  • Pregnancy-Specific beta 1-Glycoproteins / genetics
  • Pregnancy-Specific beta 1-Glycoproteins / immunology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*
  • Vaccinia virus

Substances

  • CD4 Antigens
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Pregnancy-Specific beta 1-Glycoproteins
  • Recombinant Proteins