Inflammatory reactions and the autoimmune connection
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Autoimmune disorders are driven by abnormal inflammatory reactions that cause the body’s own immune system to attack itself. These inflammatory autoimmune disorders, such as rheumatoid arthritis, ulcerative colitis and multiple sclerosis, have become more common in recent years. Rheumatoid arthritis is now the most common autoimmune disease and affects about 1.5 million adults in the United States each year.
These inflammatory disorders are characterized by an imbalance of immune cells and increased production of pro-inflammatory cytokines, which are signaling proteins that trigger or heighten inflammation. CD4+ T cells Th17 cells are a significant source of pro-inflammatory cytokines and are believed to play an essential role in inflammatory disorders.
The enzyme eukaryotic elongation factor-2 kinase (eEF2K) has vital roles in pathways that impact cellular metabolism and response to stress. Previous studies have shown that this crucial regulator of inflammation-related disorders can modulate pathways and cause hypertension, but the function of eEF2K in other inflammatory diseases, such as rheumatoid arthritis, ulcerative colitis and multiple sclerosis, is unclear.
A recent study by Dr. Jianxun (Jim) Song, professor of microbial pathogenesis and immunology at the Texas A&M University School of Medicine, explored the connections between eEF2K, CD4+ T cells, and inflammatory diseases. His team’s work highlights the role of the eEF2K protein kinase in aberrant T cell immune responses and subsequent autoimmune inflammatory disorders. Results are published in the open-access journal Signal Transduction and Targeted Therapy.
In this study, the eEF2K deficient animal model showed an increased production of pro-inflammatory Th17 cytokines, which triggered Th17-related arthritis and colitis. This enzyme also controls the transcription factor STAT3 to regulate CD4+ T cells, which play a role in the development of inflammatory autoimmune diseases. Researchers also discovered that C188-9, a small molecular inhibitor of STAT3, mitigated inflammatory bowel disease in the animal immunodeficiency model. According to Song, these results indicate that “eEF2K is essential for the survival and proliferative capacity of CD4+ T cells.”
“Our findings imply that eEF2K is a crucial regulator of effector T cells and an important determinant of autoimmunity,” Song said. “Manipulating this protein kinase may be explored as a novel approach to treating autoimmune disorders.” Song and his team are excited to bring this paper to the public and for the therapeutic potential of their work in treating autoimmune and inflammatory disorders.
