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Molecule Holds Key in Avoiding Organ Rejection
According to researchers, the molecule's action can be augmented in people with organ transplants and autoimmune disease and turned down to help fight a tumour.
Measuring endogenous levels of HLA-G dimer may also help physicians identify which transplant patients require little, if any, immune suppression.
"This is a molecule with huge potential to regulate immune response," Dr. Anatolij Horuzsko, reproductive immunologist at the Medical College of Georgia Center for Molecular Chaperone/Radiobiology and Cancer Virology.
Researchers have found that dimer appears to be the most powerful among several known forms of HLA-G at inhibiting the immune response.
The study showed that when HLA-G dimer binds with its inhibitory receptor, ILT4, it triggers a signaling pathway in which immune molecules IL-6 and STAT3 play a major role.
"Biologically this is an interaction that requires several important suppressive molecules," said Dr. Horuzsko, co-author and a faculty member in the MCG Schools of Medicine and Graduate Studies.
The researchers looked at the resulting strong signaling in culture, then measured its impact on skin graft survival in mice and found it prolonged survival.
Now, Dr. Horuzsko is working with Dr. Laura Mulloy, chief of the Section of Nephrology, Hypertension and Transplantation Medicine in the MCG School of Medicine, to see if this dimer form is at work in kidney transplant patients who avoid rejection.
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