In Vivo Expression of Recombinant Pregnancy-Specific Glycoprotein 1a Inhibits the Symptoms of Collagen-Induced Arthritis

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...

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Bibliographic Details
Published in:American journal of reproductive immunology (1989) 2014-12, Vol.72 (6), p.527-533
Main Authors: Falcón, Cristian Roberto, Martínez, Fernando F., Carranza, Franco, Cervi, Laura, Motrán, Claudia C.
Format: Article
Language:English
Subjects:
Animals
Arthritis
Arthritis, Experimental - therapy
CD4 Antigens - metabolism
Cells, Cultured
Collagen
Collagen induced arthritis
Cytokines - metabolism
Forkhead Transcription Factors - metabolism
Genetic Vectors - genetics
Humans
Immunomodulation
immunoregulation
Interleukin-2 Receptor alpha Subunit - metabolism
Male
Medical research
Mice
Mice, Inbred DBA
Pregnancy
pregnancy specific glycoproteins
Pregnancy-Specific beta 1-Glycoproteins - genetics
Pregnancy-Specific beta 1-Glycoproteins - immunology
Recombinant Proteins - genetics
Recombinant Proteins - immunology
regulatory T cells
rheumatoid arthritis
Rodents
T-Lymphocytes, Regulatory - immunology
Th1 Cells - immunology
Th17 Cells - immunology
Vaccinia virus
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Summary: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.
ISSN:1046-7408
1600-0897
DOI:10.1111/aji.12307