Enzyme keeps immune system in check
By Ruth SoRelle, M.P.H.
Until Tse-Hua Tan, Ph.D., studied animals who lacked the enzyme hematopoietic progenitor kinase 1 (HPK1), he thought the molecule – discovered in his laboratory a decade ago – increased the activity of the immune system.
To the surprise of the Baylor College of Medicine professor of immunology, when animals lacked HPK1, the signaling in the cell that marshaled the immune system forces called T-cells was enhanced along with cellular proliferation. In short, animals that lacked the protein had an enhanced immune function. When the protein was present, it slowed or decreased immune action.
Negative regulation
"This finding indicates that HPK1 negatively regulates signaling directed at T-cells and T-cell proliferation," said Tan. A report of the work carried out in his laboratory appeared in a recent issue of the journal Nature Immunology.
In fact, he said, mice that lacked this important enzyme were more susceptible to a form of autoimmune disease that mimics multiple sclerosis, a disease believed to result from the attack of the immune system on the body itself, a process called autoimmunity.
"This is consistent with the possibility that this protein plays a role in preventing autoimmune disease," he said.
In fact, he said, HPK1's strength in that role may occur because it actually affects two molecules with activity that occurs early in the cascade of events that result in activation of T-cells. By affecting these molecules, it intervenes early in the process of lymphocyte or T-cell activation and is more effective, said Tan.
Keeping T-cell activity in balance
While T-cell activity is critical in defending the body against invading bacteria and other organisms, it is also important to shut that activity off when it has accomplished its task and before it starts to attack the body's own tissues, said Tan, who is also a faculty member in the BCM Graduate School of Biomedical Sciences. HPK1 appears to play a role in halting the T-cell action.
Others who took part in the research include: Drs. Jr-Wen Shui, Jonathan S. Boomer, Jin Han, Jun Xu, Gregory A. Dement and Guisheng Zhou, all of BCM.
Support for this work came from the National Institutes of Health and the American Heart Association Texas Affiliate.
(Nat Immunol. 2007 Jan;8(1):84-91. Epub 2006 Nov 19)
