Researchers at the Catholic University of Korea said they discovered a novel cytokine immune protein, p40, and EB13, that can control immune T cells for the treatment of intractable autoimmune diseases like rheumatoid arthritis.
The interleukin (IL)-12 cytokine family is associated with T cells that activate or inhibit autoimmune diseases, and are generally heterogeneous which include two protein units p40 and EBI3. Particularly, the p40 homologous dimer - a structure containing two similar units- inhibits IL-23 inflammatory signaling, an essential mechanism for the initiation and progression of inflammatory arthritis.
Accordingly, the research team led by Professor Cho Mi-la and first author Lee Seon-yeong assumed the presence of the p40-EBI3 heteromer in the unit and investigated its role in immune control.
The researchers confirmed that the administration of the p40-EBI3 protein inhibited the disease activity of rheumatoid arthritis and the expression of inflammatory cytokines IL-17, IL-1, IL-6, and TNF-α immune cells. Additionally, the p40-EBI3-Fc fused protein significantly inhibited the differentiation of Th17 cells in vitro and increased the activity of CD4+CD25+Foxp3+ regulatory Treg cells.
Consequently, the research team confirmed the presence of p40-EBI3 in dendritic cells which improved the disease and inflammation of rheumatoid arthritis in vivo and in vitro. Therefore, the research team suggested that these proteins, as a novel anti-inflammatory cytokine, are involved in inhibiting immune responses through the increase of Treg cells by p40-EBI3 and inhibition of Th17, another immune cell, and osteoclast formation.
Furthermore, diseased Th17 cells and regulatory Treg cells can selectively differentiate and develop through the regulation of transcription factors, STAT3 and STAT5. However, the p40-EBI3 protein activates the STAT5 transcription factor in immune T cells to increase the activity of regulatory T cells (Tregs).
Professor Cho Mi-la said, "Most drugs in the existing autoimmune disease treatment market have been developed focusing on immunosuppression, but we are proud that our research has confirmed that the p40-EBL3 complex can induce immune regulation or suppression."
This study was published in Nature, Cellular and Molecular Immunology, on Tuesday.