Without the STAT3 gene, a pivotal class of immune cells known as ‘T follicular helper cells’ cannot develop.
T follicular helper cells enable B cells, one of several kinds of white blood cell in our bodies, to make long-lived high-potency antibodies. Not only do these antibodies fight current infections, but ‘Memory B cells’ created in the process instantly recognise the same invaders in the future.
Dr Cindy Ma and Associate Professor Stuart Tangye from Sydney’s Garvan Institute of Medical Research have demonstrated that T cells from patients with mutations in the STAT3 gene have an impaired ability in producing IL-21, an essential growth factor in promoting the generation of memory B cells and protective antibodies. Their study, based on a total of 31 patients with immunodeficient diseases (14 of whom had a STAT3 mutation), is published in Blood, now online.
“This is the first study to demonstrate the critical nature of the STAT3 gene in T-cell dependent antibody-mediated immune responses in people,” said Associate Professor Tangye.
“STAT3 enables a chain of other events, including activation of complex signaling pathways, without which our T cells can’t help our B cells do their job.”
“Robust antibody responses are critical for our health. When they’re absent or defective, people suffer from crippling and recurrent infections. When they’re exaggerated, people can develop autoimmune diseases such as lupus, Type 1 diabetes or rheumatoid arthritis.”
“Anti-cancer drugs already exist that inhibit the function of STAT3. In the case of autoimmunity, where the body attacks its own tissues, the immune system is on overdrive, working too hard and making mistakes. We need to find a way to wind that back – and we believe that blocking the STAT3 gene, or its effects, might do just that.”
“While these are early findings, we believe their potential is evident.”
The Garvan Institute of Medical Research was founded in 1963. Initially a research department of St Vincent’s Hospital in Sydney, it is now one of Australia’s largest medical research institutions with over 500 scientists, students and support staff. Garvan’s main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation and Neuroscience. Garvan’s mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan’s discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.
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