2006 Gender Matters
There has long been speculation as to why females are so much more likely than males to get lupus, with nine women for every one male being affected.
With her LRI grant, Dr. Pernis set out to investigate the mechanisms by which the female sex steroid, estrogen, controls the expression of a new molecule that her laboratory was among the first to identify: IBP.
According to preliminary findings, IBP is critical for the function of the T cells that inappropriately regulate and activate the immune system in lupus. Mice deficient in IBP develop a lupus-like syndrome that, like lupus in humans, affects many more females than males.
Discovery: A Key Mechanism in the Cause and Development of Autoimmunity
In a key 2008 Immunity article, Dr. Pernis and colleagues highlight just how critical the role of the IBP protein is in preventing a sequence of reactions that leads to inflammation and autoimmunity.
They also show how lupus and other autoimmune processes can spontaneously develop when IBP is absent.
Without IBP in its role as something of a “control cop” in molecular pathways of the immune system, they demonstrated, for example, that white blood “T” cells charged with responding to infected or malignant cells start pumping out damaging inflammatory substances (interleukin-17 and 21).
By uncovering IBP’s importance in keeping things in order in the immune system in this and other ways, the researchers can now focus on finding ways to manipulate or reintroduce it.
“These studies provide crucial insights into the mechanisms required for the proper control of immune responses,” said study co-author Alessandra Pernis, M.D., “as well as potentially guiding the development of innovative strategies to target systemic autoimmune diseases like lupus.”
“The funding provided by the LRI was instrumental in supporting my studies.” – Dr. Pernis
RF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor. Chen Q, Yang W, Gupta S, Biswas P, Smith P, Bhagat G, Pernis AB. Immunity. 2008 Dec;29(6):899-911. Epub 2008 Dec 8.