Greg E. Lemke, PhD
The Salk Institute for Biologic Studies, La Jolla, CA
With funding from the LRI, Dr. Lemke pursued a novel idea: that a curious family of “TAM” receptors might function as a core ‘control switch’ over the immune system’s inflammatory response.
He was on target, and reported finding this entirely new and powerful molecular switch in the journal Cell in December 2007.
Now that this switch has been identified, new methods can be pursued to shut down uncontrolled inflammation, restore immune system regulation, and treat chronic autoimmune disorders such as lupus.
In autoimmunity, the immune system designed to fend off outside invaders mistakenly mounts an out-of-control destructive inflammatory attack against the body’s own tissues and organs.
In his study, Dr. Lemke builds upon findings that he and his team previously reported, when he noticed that mice genetically engineered to be born without a tiny family of three receptors—TAM receptor tyrosine kinases—developed an autoimmune illness similar to lupus in humans.
In the Cell article, Dr. Lemke illustrates how these “TAM” receptors, under normal circumstances, are so critical in stopping the immune system from mounting an out-of-control inflammatory response against invading viruses and bacteria. When chemical messengers (cytokines) prompt immune cells to attack, he explains, they also activate TAM receptors, which then alert the cells to no longer react to the cytokines. This keeps the immune system orderly as well as relatively tranquil.
But in people with lupus and certain other autoimmune illnesses, the TAM signalling network may be seriously compromised. The switch to inhibit inflammation on this network may be absent—thereby resulting in immune system pandemonium.
People with lupus tend to have low levels of a blood factor (proteins S) that TAM receptors require to carry out their job. Giving modified versions of protein S, or its related TAM activator Gas6, to people with lupus may represent a means of halting the immune system destruction of precious organs and tissues. “This is definitely something we intend to investigate,” Dr. Lemke said.
“Without the LRI, this project would have stopped—and a fundamental discovery in immunology would not have happened.”
– Dr. Lemke
TAM receptors are pleiotropic inhibitors of the innate immune response. Rothlin CV, Ghosh S, Zuniga EI, Oldstone MB, Lemke G. Cell. 2007 Dec 14;131(6):1124-36.
Dr. Lemke has been awarded $1.4 million from the NIH and others to explore exciting new approaches to mastering this switch—shutting down the uncontrolled inflammation of lupus and other autoimmune illnesses by restoring immune system regulation.
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