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Source: Research News  Nov 05, 2020  2 years, 10 months, 3 weeks, 4 days, 10 hours, 58 minutes ago

Research News: Yale Researchers Claim To Uncover New Mechanism Of Immune-Cell Activation

Research News: Yale Researchers Claim To Uncover New Mechanism Of Immune-Cell Activation
Source: Research News  Nov 05, 2020  2 years, 10 months, 3 weeks, 4 days, 10 hours, 58 minutes ago
Research News:  In a new study by Yale Cancer Center, researchers have identified the short endosomal protein interferon-inducible transmembrane protein 3 or IFITM3 as a central amplifier to supercharge activation of immune cells.

The IFITM3 proteins functions like glue to rapidly assemble and tighten up large complexes of signaling molecules that together generate the activation signal. Without IFITM3, antibody-producing B-cells cannot vigorously fight infections and do not generate immunological "memory" of the infectious particles that they encountered.
The study findings are published in the journal Nature.
Thailand Medical News had already covered the roles that IFITMs 1 to 3 play in the immune system especially with regards to the SARS-CoV-2 context in late August.,-new-study-claims-that-ifns-actually-may-enhance-viral-invasio
Typically when antibody-producing immune cells encounter infectious pathogens for the first time, they engage a signal cascade to generate a massive activation signal within seconds. The mechanisms underlying this acute initial activation have not been fully understood till now (or as so claimed by Yale researchers)
Dr Markus Müschen, MD, Ph.D., Director of the Center of Molecular and Cellular Oncology, Arthur H. and Isabel Bunker Professor of Medicine (Hematology) at Yale Cancer Center, and senior author of the study told Thailand Medical News, "Genetic deletion of IFITM3 in B-cells did not affect their survival, but when the B-cells encountered foreign pathogen, their response was sluggish. Unexpectedly, we discovered IFITM3 at the center of a new signaling cascade that B-cells in the immune system need to mount a vigorous immune response."
The novel IFITM3 signal amplifier unfortunately functions as a double-edged sword. While this mechanism helps immune cells to fight infections, the new study also showed that cancer cells use the exact same mechanism for activation and explosive growth.
Dr Müschen added, "Studying patients with B-cell malignancies in three clinical trials, we found high expression of IFITM3 among the strongest predictors of poor clinical outcome. This was unexpected because this tiny protein was known ability to make cell membranes more rigid, but we had no idea what its function could be in B-cell tumors."
However on the upside, loss of IFITM3 did not only impact immune cells, but also headed off the development of cancer. In the absence of IFITM3, normal cells that acquire cancer-causing mutations are protected from malignant transformation and cannot initiate the critical signal cascade that is needed for cancerous growth.
Dr Müschen added, "Interestingly, the first step of this cascade, the initial activation of IFITM3 can be blocked by kinase inhibitors that are already available in the clinic. Going forward, we will test whether some of these kinase inhibitors are effective in blocking IFITM3-dependent signal amplification in cancer."
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