A new signaling pathway of the immune system is elucidated

March 31, 2011

A new signaling pathway, which is important for the regulation of the immune response and inflammation, was discovered by an international team of scientists led by prof Ivan Dikic from the Goethe University, Frankfurt, Germany. The scientists studied the involvement of ubiquitin, a universally present signaling protein in the cell. In today's issue of the scientific journal "Nature" the scientists report a novel type of modified ubiquitin chains involved in regulation of various processes within the cell.

The researchers have shown that linear ubiquitin, where ubiquitin proteins are attached to each other in a head to tail fashion, regulates signaling cascades initiated by cytokine receptors at the cell membrane. Cytokines are essential for the proper immune response - e. g. tumor necrosis factor (TNF-alpha) alpha is released mainly by the macrophages and plays an important role in local and body-wide inflammation.

When a cytokine docks on the receptor of a cell, it induces a signaling cascade in many cell types, which transmits a signal to the nucleus - the DNA centre of the cell. After cytokine activation of its receptor, the linear ubiquitin ligase complex (LUBAC), which links ubiquitin into head-to-tail chains, is activated at the start of this cascade. This enzyme stimulates nuclear factor kappaB (NF-kappaB), which coordinates the expression of important genes for the immune response, including the production of antibodies. However, how the molecules of this cascade function in detail and which structures interact is still under investigation.

The Dikic group solved an integral part of this puzzle. Sharpin, a protein containing a Ubiquitin-like and Ubiquitin-binding domain (UBD), constitutes a key component of the linear Ubiquitin ligase complex. Using animal models, they show that a lack of Sharpin causes heavy inflammation of numerous organs and in particular the skin. This is characterized as chronic proliferative dermatitis with death of keratinocytes, the predominant cells of the epidermis in charge of protecting the skin against environmental damage. This effect is dependent on the TNF signaling pathways.

The research reported allows us to reshape our thinking about how chronic proliferative dermatitis arises in humans, as well as opening new avenues of therapeutic intervention in the TNF-alpha signalling pathway. Moreover, a potential source of this disease may arise from mutations in a critical region of the linear ubiquitin ligase complex (LUBAC) allowing identification of patients that may respond well to targeted therapy. "In patients suffering from chronic proliferative dermatitis with unclear origin, it is now possible to specifically look for a mutation in LUBAC components", suggests Ivan Dikic.
-end-


Goethe University Frankfurt

Related Immune Response Articles from Brightsurf:

Boosting chickens' own immune response could curb disease
Broiler chicken producers the world over are all too familiar with coccidiosis, a parasite-borne intestinal disease that stalls growth and winnows flocks.

Cells sacrifice themselves to boost immune response to viruses
Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection.

Children's immune response more effective against COVID-19
Children and adults exhibit distinct immune system responses to infection by the virus that causes COVID-19, a finding that helps explain why COVID-19 outcomes tend to be much worse in adults, researchers from Yale and Albert Einstein College of Medicine report Sept.

Which immune response could cause a vaccine against COVID-19?
Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition.

Obesity may alter immune system response to COVID-19
Obesity may cause a hyperactive immune system response to COVID-19 infection that makes it difficult to fight off the virus, according to a new manuscript published in the Endocrine Society's journal, Endocrinology.

Immune response to Sars-Cov-2 following organ transplantation
Even patients with suppressed immune systems can achieve a strong immune response to Sars-Cov-2.

'Relaxed' T cells critical to immune response
Rice University researchers model the role of relaxation time as T cells bind to invaders or imposters, and how their ability to differentiate between the two triggers the body's immune system.

A novel mechanism that triggers a cellular immune response
Researchers at Baylor College of Medicine present comprehensive evidence that supports a novel trigger for a cell-mediated response and propose a mechanism for its action.

Platelets exacerbate immune response
Platelets not only play a key role in blood clotting, but can also significantly intensify inflammatory processes.

How to boost immune response to vaccines in older people
Identifying interventions that improve vaccine efficacy in older persons is vital to deliver healthy ageing for an ageing population.

Read More: Immune Response News and Immune Response Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.