Averil Ma
UCSF immunology researcher Averil Ma, MD, has determined an important role for a specific protein that blocks cell death, which is often caused by an inflammatory protein. This biological mechanism might play a role in the death of immune T cells when they are infected with HIV, the AIDS virus, according to Ma.
Furthermore, emerging evidence suggests that inherited genetic variations in the protein, called ABIN-1, might make some people more susceptible to autoimmune diseases such as lupus, psoriasis and rheumatoid arthritis, Ma says.
ABIN-1 blocks cell death and promotes cell survival. In the Dec. 7 online edition of the scientific journal Nature, Ma, the Rainin Distinguished Professor in Inflammatory Bowel Disease at UCSF, describes how ABIN-1 blocks cells death caused by the inflammatory molecule TNF. ABIN-1 interferes with a biochemical chain reaction triggered by attachment of TNF to its receptor protein, called a “death receptor.”
“The paper defines a potent, new role for this molecule,” Ma says.
ABIN-1 is believed to be present and working in cells throughout the body, Ma explains. Ma’s lab team targeted ABIN-1 for elimination in mice. Mouse embryos that failed to make ABIN-1 died before birth. TNF can be secreted by many types of cells, but is secreted “most robustly” by immune cells, Ma says. It seems odd that an inflammatory molecule such as TNF is routinely present in embryos. “Why you need to cause physiological inflammation in that setting is unclear,” Ma says. “Unfortunately, it has not been explored adequately.”
What this means for the well-being of humans may take longer to unravel.
“One tantalizing prospect is related to the observation that infected T cells from AIDS patients don’t survive well and undergo programmed cell death,” Ma says. The weakening of the immune system due to T-cell death in HIV infection has resulted in millions of deaths due to opportunistic infections. HIV includes a protein that binds to ABIN-1 in T cells. Ma’s new findings raise the possibility that the reduction of ABIN-1 in T cells by HIV might be making these immune cells more likely to die, Ma suggests.
TNF plays a role in autoimmune diseases such as lupus, psoriasis, rheumatoid arthritis and many others. According to Ma, despite the emerging evidence that genetically inherited variations in ABIN-1 play a role in susceptibility to autoimmune diseases, “it’s too soon to say that genetic variations in ABIN-1 cause the cells in certain individuals to be more likely to die due to inflammation. But that is one of the novel implications of our study.”
