Nav: Home

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018

A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

The research led by Enrico Petretto, Associate Professor at Duke-NUS Medical School (Duke-NUS), along with Dr Jacques Behmoaras at Imperial College London and collaborators from University College London in the UK, established for the first time a decisive link between immune cells, specifically the macrophages derived from SSc patients and systemic sclerosis. The study also demonstrated the role played by macrophages in the development of the disease due to known genetic factors, such as the case of the sussceptibility gene GSDMA, which has been involved in cell death in the skin and was associated to the disease in 4,436 SSc patients, but whose function in macrophages from SSc patients was unclear.

Previous genetic studies have found various genes associated with SSc susceptibility, but so far, it is not known for certain which type of cells are crucial for the development of the disease. The team used advanced transcriptomic and genetic analyses, which included RNA-sequencing and systems-genetics in macrophages of 57 SSc patients, and established decisively the role for hundreds of macrophage genes in the development of SSc. Their discovery will point the way for researchers looking to develop new therapies for SSc.

"In the long quest for finding therapies for systemic sclerosis, our findings have implications for understanding the genetic basis of the disease, and we believe our discovery will prompt detailed functional studies in macrophages and immune cells, hopefully providing a starting point to develop greatly needed treatments for this disease" explained Professor Petretto, co-lead principal investigator and coordinator of the study.

Published today in the Annals of Rheumatic Diseases (ARD) -- the highest ranked journal in Rheumatology -- in addition to confirming many genes previously implicated in the genetic predisposition to the disease, the study further discovered hundreds of genes that are previously not known to be associated with SSc. This provides a new starting point to better understand the disease aetiology, its genetic causes and develop therapies for SSc.

"Investigating how genetic variation is responsible for systemic sclerosis is a colossal task. By looking at immune cells such as macrophages, we can generate specific hypotheses that will allow us to understand how these cells cause damage," added Dr Jacques Behmoaras, co- lead principal investigator from Centre for Complement and Inflammation Research, Imperial College London.
-end-
The study was supported by the Medical Research Council, UK, the National Research Foundation Singapore under its Cooperative Basic Research Grant (NMRC/CBRG/0106/2016) administered by the Singapore Ministry of Health's National Medical Research Council and Duke-NUS Medical School, as well as by the Arthritis Research UK, Scleroderma & Raynaud's UK and the Royal Free Charity, UK.

Note:

'Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk' will be published in the Annals of Rheumatic Diseases online at 0600 GMT of 18 January 2018 (DOI: 10.1136/annrheumdis-2017-212454)

Duke-NUS Medical School

Related Immune Cells Articles:

Immunology: How ancestry shapes our immune cells
A genetic variant that is particularly prevalent in people of African ancestry confers protection against malaria.
Immune cells derived from specialised progenitors
Dendritic cells are gatekeepers of Immunity. Up to now dendritic cell subtypes were thought to develop from one common progenitor.
Comprehensive atlas of immune cells in renal cancer
Researchers from the University of Zurich have individually analyzed millions of immune cells in tumor samples from patients with renal cell carcinoma.
When liver immune cells turn bad
A high-fat diet and obesity turn 'hero' virus-fighting liver immune cells 'rogue,' leading to insulin resistance, a condition that often results in type 2 diabetes, according to research published today in Science Immunology.
New role for immune cells in preventing diabetes and hypertension
Immune cells which are reduced in number by obesity could be a new target to treat diseases such as type 2 diabetes and hypertension that affect overweight people, according to a collaborative study between the University of Manchester, Lund University and the University of Salford.
Why male immune cells are from Mars and female cells are from Venus
Michigan State University researchers are the first to uncover reasons why a specific type of immune cell acts very differently in females compared to males while under stress, resulting in women being more susceptible to certain diseases.
Immune therapy scientists discover distinct cells that block cancer-fighting immune cells
Princess Margaret Cancer Centre scientists have discovered a distinct cell population in tumours that inhibits the body's immune response to fight cancer.
Opioids produce analgesia via immune cells
Opioids are the most powerful painkillers. Researchers at the Charité -- Universitätsmedizin Berlin have now found that the analgesic effects of opioids are not exclusively mediated by opioid receptors in the brain, but can also be mediated via the activation of receptors in immune cells.
Oddly shaped immune cells cause fibrosis
Scientists at the Immunology Frontier Research Center (IFReC) at Osaka University, Japan, report a new group of monocytes they call SatM.
New system developed that can switch on immune cells to attack cancer cells
Researchers have developed an artificial structure that mimics the cell membrane, which can switch on immune cells to attack and destroy a designated target.

Related Immune Cells Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...