Immune hematology

The researches find that the and  DNA-repair proteins associated with breast, ovarian prostate; and pancreatic cancers interacts with a multipart; molecular complex that is also responsible for regulating the immune system. When certain players in this pathway go awry; autoimmune disorders, like lupus; can arise.

The DNA-repair proteins

Now, researchers in the Perelman School of Medicine at the University of Pennsylvania and colleagues at the University of Leeds, United Kingdom; have deciphered the structure of the complex and have found new molecular targets for fighting autoimmunity.

Their findings are publish this week in Nature. An immune system is a collection of biological processes within an organism that protects against disease by identifying and killing pathogens and tumour cells. Therefore It detects a wide variety of agents, from viruses to parasitic worms; and needs to distinguish them from the organism’s own healthy cells and tissues in order to function properly.

Collection of biological processes

Detection is complicated as pathogens can evolve rapidly; producing adaptations that avoid the immune system and allow the pathogens to successfully infect their hosts. “The important association between this complex and the immune system originally came about because my lab focuses on how BRCA1/2 function in DNA damage responses; and we realized that immune signaling entailed similar events that are governed by some of the same players involved in BRCA function;” said co-senior author Roger Greenberg, MD, Ph.D., a professor of Cancer Biology and director of Basic Science at the Basser Center for BRCA.

An enzyme that functions with BRCA1 to repair damaged DNA also exists within a separate complex called BRISC to regulate immune signaling. Greenberg’s team explored the relationship between BRISC and immune cell surface receptors to better understand the symptoms of lupus and other autoimmune diseases.

Repair damaged DNA

The overproduction of immune cells, and their signaling compounds called cytokines; stirs up hyper-inflammation that can cause substantial tissue damage; an effect of many autoimmune disorders. Lupus patients, in particular, produce too much of the cytokine interferon; therefore a natural chemical that signals to the immune system in ways that can exacerbate inflammation.

Greenberg collaborated with University of Leeds structural biologist Elton Zeqiraj to figure out the structure of the molecular complex using cryo-electron microscopy (cryo-EM). Because Their findings revealed a fascinating molecular; mechanism that connected BRISC to an enzyme involved in metabolism called serine hydroxymethyl transferase 2 (SHMT2). SHMT2 guides reactions essential for basic body functions; such as building blocks for proteins and DNA, after being activated by a form of vitamin B6.