Navigation Links
Immune cell death defects linked to autoimmune diseases

Melbourne researchers have discovered that the death of immune system cells is an important safeguard against the development of diseases such as type 1 diabetes, rheumatoid arthritis and lupus, which occur when the immune system attacks the body's own tissues.

The finding suggests that these so-called autoimmune diseases could be treated with existing medications that force long-lived immune system cells to die.

In the development of the immune system, some cells are produced that have the potential to attack the body's own tissues, causing autoimmune disease. The death of these 'self-reactive' immune cells through a process called apoptosis is an important safeguard against autoimmune disease.

But Dr Kylie Mason, Dr Lorraine O'Reilly, Dr Daniel Gray, Professor Andreas Strasser and Professor David Huang from the Walter and Eliza Hall Institute, and Professor Paul Waring from the University of Melbourne have discovered that when immune cells lack two related proteins, called Bax and Bak, the cells can attack many healthy tissues, causing severe autoimmune disease. The research is published online today in the journal Proceedings of the National Academy of Sciences.

Bax and Bak are members of the 'Bcl-2 protein family', a large group of proteins that control cell death. Dr O'Reilly said it was thought that Bax and Bak acted like an irreversible switch in cells, determining when cells die by apoptosis. In healthy cells, Bax and Bak are in an 'inactive' form, but when cells are under stress or receive external signals instructing them to die, Bax and Bak switch into an 'active' form that starts the destruction of the cell by apoptosis. Without Bax and Bak, cells are highly protected against apoptosis.

Dr O'Reilly said that some immune cells that lacked the proteins Bax and Bak were able to attack healthy tissues in many organs of the body. "Normally, these 'self-reactive' immune cells are deleted during development," she said. "In the absence of Bax and Bak, enough self-reactive cells survive development to persist in the body and cause autoimmune disease in organs such as the kidneys (glomerulonephritis), similar to what is seen in the most severe form of lupus.

"Our findings confirm that defective apoptosis of immune cells can cause autoimmune disease, and that Bax and Bak are important determinants of immune cell death. We were also interested to see that, in our model, loss of Bak on its own was sufficient to cause autoimmune disease, albeit to a lesser extent than losing both Bak and Bax. This supports a recent discovery that humans with mutations in the BAK gene are predisposed to certain autoimmune diseases."

The research provides hope for people with autoimmune diseases as Bax and Bak activity can be triggered by a new class of potential anti-cancer agents, called BH3-mimetics, which are currently in clinical trials for certain types of leukaemia in Melbourne, Dr O'Reilly said. "Our findings suggest that BH3-mimetics might be an exciting new option for treatment for autoimmune conditions, by activating Bax and Bak and making the self-reactive immune cells which are causing the autoimmune disease to die," she said.


Contact: Vanessa Solomon
Walter and Eliza Hall Institute

Related biology news :

1. Immune system molecule with hidden talents
2. Protein structure: Immune system foiled by a hairpin
3. La Jolla Institute identifies molecular switch enabling immune cells to better fight disease
4. Loneliness, like chronic stress, taxes the immune system
5. Smile: Gingivitis bacteria manipulate your immune system so they can thrive in your gums
6. New insights into how immune system fights atherosclerosis
7. Alzheimers disease: Cutting off immune response promises new approach to therapy
8. New technique could make cell-based immune therapies for cancer safer and more effective
9. Engineered immune cells produce complete response in child with an aggressive pediatric leukemia
10. Steroid hormone receptor prefers working alone to shut off immune system genes
11. Combining two genome analysis approaches supports immune system contribution to autism
Post Your Comments:
Related Image:
Immune cell death defects linked to autoimmune diseases
(Date:11/18/2015)... new scientific discoveries deepen our understanding of how cancer ... challenges in better using that knowledge to guide treatment ... children continue to survive pediatric cancer, that counseling may ... John M. Maris, M.D ., a pediatric oncologist ... --> John M. Maris, M.D ., ...
(Date:11/17/2015)... , Nov. 17, 2015  Vigilant Solutions announces today ... its Board of Directors. --> ... recently retiring from the partnership at TPG Capital, one ... with over $140 Billion in revenue.  He founded and ... all the TPG companies, from 1997 to 2013.  In ...
(Date:11/12/2015)... 2015  Arxspan has entered into an agreement ... for use of its ArxLab cloud-based suite of ... partnership will support the institute,s efforts to electronically ... information internally and with external collaborators. The ArxLab ... the Institute,s electronic laboratory notebook, compound and assay ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , Nov. 25, 2015 Orexigen® Therapeutics, ... will participate in a fireside chat discussion at the ... New York . The discussion is scheduled for ... .  A replay will be available ... Contact:McDavid Stilwell  , Julie NormartVP, Corporate Communications and ...
(Date:11/24/2015)... Nov. 24, 2015  Asia-Pacific (APAC) holds the ... (CRO) market. The trend of outsourcing to low-cost ... but higher volume share for the region in ... however, margins in the CRO industry will improve. ... ( ), finds that the market ...
(Date:11/24/2015)... Halozyme Therapeutics, Inc. (NASDAQ: HALO ) will be ... York on Wednesday, December 2 at 9:30 a.m. ET/6:30 ... CEO, will provide a corporate overview. th Annual ... 1:00 p.m. ET/10:00 a.m. PT . Jim Mazzola , ... corporate overview. --> th Annual Oppenheimer Healthcare Conference ...
(Date:11/24/2015)... Florida (PRWEB) , ... November 24, 2015 , ... ... biggest event of the year and one of the premier annual events for ... and ran from 8–11 November 2015, where ISPE hosted the largest number of ...
Breaking Biology Technology: