A host of immunological insights in just 3 months

2 April 2019
Dirk Elewaut’s team puts the pedal to the metal for multiple nature communications publications

Scientists in the lab of Dirk Elewaut (VIB-UGent Center for Inflammation Research) are no strangers to challenging schedules. Achieving three separate publications in Nature Communications between November 2018 and January 2019, Dirk’s team was hard at work during the holiday season, bringing the latest immunity discoveries to the wider scientific world.

The last handful of months have seen new studies emerge from the Dirk Elewaut lab that address key questions in immunology related to chronic joint inflammation, immune-regulating stress responses and the role of rare immune cells in spondyloarthritis.

ARTHRITIS DOESN’T AFFECT ALL JOINTS
Rheumatoid arthritis and spondyloarthritis are painful and disabling conditions that cause inflammation in joints and other tissues, with each condition affecting 1% of the population. A key historical sticking point in the study of arthritis, why particular joints are more affected than others, has finally been answered by Isabelle Cambré and Dirk Elewaut. “The reason why certain joints are more susceptible to arthritis is mainly a biomechanical one,” Isabelle explains. “We studied bone erosions caused by inflammation to identify musculoskeletal ‘hot spots’ that are more prone to the debilitating effects of the disease.”
However, other factors are also at play in the so-called ‘patchy’ distribution of arthritic joint inflammation. “Mechanical stress releases inflammatory mediators, such as chemokines, which bring white blood cells into the area and cause the tissue damage,” continues Isabelle. “Now that we have unveiled these insights, we are in the process of studying the underlying molecular pathways of the process – it’s a unique area of research that combines inflammation and mechanobiology.”

INVOLVEMENT OF KILLER T CELLS IN DIFFERENT DISEASES
The Nature Communications study led by Srinath Govindarajan from Dirk’s lab, zeroed in on the remarkable ability of immune cells – natural killer T cells – to protect the body against diseases, cancer, infections and more.

“Natural killer T cells are such efficient fighters because they can generate huge amounts of cytokines, which allow different types of immune cells to communicate with each other,” Srinath asserts. “Our study shed more light on how natural killer T cells make these molecules.”

“Our team found that a specific stress-related response controls the function of these cells – and not other types of immune cells,” Dirk elaborates. “It’s a very specific mechanism. We believe that modulating this stress response could lead to new therapies for immune diseases driven by natural killer T cells.”

A DIFFERENCE IN TREATMENT OF CHRONIC RHEUMATIC DISORDERS
When it comes to treating spondyloarthritis, a therapy called IL-17 cytokine blockade has greatly improved the lives of these patients. Rheumatoid arthritis, another type of chronic arthritis, failed to respond when treated with the same therapy. “There is a difference between the clinical presentations of spondyloarthritis and rheumatoid arthritis, and also in their responses to treatment,” says lead researcher Koen Venken. “But these observations have never been explained. We discovered that there are phenotypical differences between rare immune cells – known as unconventional Tcells – in SpA and RA patients, changing the way they mediate inflammation.”

“Our results demonstrate that these specialized immune cells play major roles in inflammatory diseases – and also that human immune cells are even more biologically diverse (i.e. at the transcriptome level) than we realized,” Dirk sums up. “The transcriptional details that we uncovered may reveal effective new treatment avenues for a range of inflammatory disorders.”

Cambré et al., Nature Communications 2018
Govindarajan et al., Nature Communications 2018
Venken et al., Nature Communications 2019


 Isabelle Cambré
 Koen Venken
Srinath Govindarajan​ 
 Dirk Elewaut