Allergic And Autoimmune Diseases Connected, Implications For The Development Of New Therapies To Target Cancer
"It was exciting to have the opportunity to apply cutting-edge technology using the findings of the Human Genome Project," said NIAMS (National Institute of Arthritis and Musculoskeletal and Skin Diseases) Scientific Director John O'Shea, M.D. "Using this technology, we were able to map the action of Bach2 across all genes. This gave us a clearer understanding of Bach2's key role in the immune system."
"The finding that a single component of a mouse's immune system, which the studies were done on, plays such a broad role in regulating immune functions may explain why people with allergic and autoimmune diseases commonly have alterations in the Bach2 gene," said National Cancer Institute (NCI) postdoctoral fellow and researcher Rahul Roychoudhuri, M.D. "This may be the first step in developing novel therapies for these disorders."
Study co-author Nicholas P. Restifo, tenured senior investigator in the National Cancer Institute of the National Institutes of Health (NIH), suggested that these findings have implications for cancer as well, since cancers use regulatory T cells to prevent their own destruction by antitumor immune responses. He and his colleagues are now working toward manipulating the activity of the Bach2 gene with the goal of developing a new cancer immunotherapy. As this study was conducted in mice, it must be replicated in humans before its findings can be applied in a clinical setting.
Further research into Bach2 and its implications for cancer treatment will be continued by the team - a collaboration from the NIH and Sidra Medical and Research Center in Doha Qatar. "Our aim is to extend this observation toward its practical application to modulate the outcome of immune diseases by genetically regulating the function of Bach2 or other factors that regulate immune cell function," said Sidra's Chief Research Officer Dr. Francesco M. Marincola, who was involved in the study. "At Sidra we will carry out research to broaden the scientific community's understanding of a broad range of diseases that affect women and children around the world. I am delighted that we will be able to use our unique resources and expertise to expand this vital piece of research."
Sidra plans to develop a facility where reprogrammable cell therapy can be conducted. A delegation led by David F. Stroncek, MD, Chief of the Cell Processing Section at the NIH will visit Sidra in June to begin discussion on collaboration in the creation of a reprogrammable cellular therapy facility, which will become a resource for Sidra's local, regional and international partners and collaborators.
In autoimmune diseases, the immune system attacks normal cells and tissues in the body that are generally recognized as "self" and do not usually trigger immune responses in patients without autoimmune diseases. Autoimmunity can arise as a consequence of abnormal immune responses in infectious diseases and cancer. The immune system is comprised of a variety of cell types that must act in unison to maintain a healthy balance. White blood cells called 'CD4+ T cells' play a dual role within the immune system. Some CD4+ T cells activate immune responses, whereas others, called regulatory T cells, function in the opposite direction by constraining immune responses. This duality is important because uncontrolled immune responses may result in immune system attacks against the body's own cells and tissues, which occurs in allergic and autoimmune diseases. One of the hallmarks of uncontrolled immune responses is excessive tissue inflammation. Although tissue inflammation is a normal part of immune responses, excessive inflammation can lead to tissue and organ damage and may be potentially lethal. How CD4+ T cells become either activating/inflammatory or regulatory is not well understood, according to the researchers.
Sidra Medical and Research Center
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