Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

By studying blood vessels at single cell resolution, Professor Jagdeep Nanchahal and colleagues found that in Dupuytren’s disease, a fibrotic disorder of the hand, the vasculature is key to orchestrating the development of human fibrosis.

Blood cells

The team has previously shown that development of myofibroblasts, the cells responsible for deposition of the excessive matrix and contraction, is dependent on production of tumour necrosis factor (TNF) by local immune cells. The research, published in PNAS showed that endothelial cells lining the blood vessels modulate the activity of immune regulatory fibroblasts, which secrete mediators that attract the immune cells. They also identified that a potential myofibroblast precursor cell that is contained within a compartment of cells called pericytes that wrap around the blood vessel wall.

First author on the paper, Dr Thomas Layton, who started the work the work as a Kennedy DPhil student at the Kennedy Institute said: "This study illustrates the potential of using state of the art molecular biology techniques to relatively under studied diseases."

Fibrotic diseases, such as idiopathic pulmonary fibrosis, liver cirrhosis and chronic kidney disease, all result from excessive scarring of tissues leading to progressively worsening organ function. Although these diseases have high morbidity and mortality in the Western world, research has been limited by difficulty accessing tissues at the earliest stages of disease. In contrast, in Dupuytren's disease, affected tissues from the palm of the hand are relatively easy to obtain, and can provide clues into fibrotic pathways and possible approaches to slow down or halt disease.

"Animal models fail to recapitulate all aspects of human fibrosis," said Professor Nanchahal. "The pathways we identified using tissue from patients with Dupuytren's disease also appear to pertain to other human fibrotic diseases, such as idiopathic pulmonary fibrosis."

The work was supported by an Oxford-BMS/Celgene fellowship, Royal College of Surgeons of England and British Society for Surgery of the Hand.

Similar stories

Breakthrough in treatment for Dupuytren’s disease

Injection of the anti-TNF drug adalimumab into Dupuytren’s disease nodules is effective in reducing nodule hardness and nodule size.

Defining the role of resident memory B cells in the fight against influenza

Researchers at the Kennedy Institute of Rheumatology have used 3D and live-imaging to show how resident memory B cells boost antibodies to fight influenza.

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

The COVID-19 Multi-omic Blood Atlas (COMBAT) has identified blood hallmarks of COVID-19 involving particular immune cell populations and their development, components of innate and adaptive immunity, and connectivity with the inflammatory response.

Behind enemy lines: research finds a new ally in the fight against cardiovascular disease hidden within the vessel wall itself

A new study reveals the existence of a powerful ally in the fight against cardiovascular disease, a protective subset of vascular macrophages expressing the C-type lectin receptor CLEC4A2, a molecule which fosters "good" macrophage behaviour within the vessel wall.

A drug being trialled to treat cancer, could be the key to reducing gut inflammation

Published in Nature Communications, a new study reveals a new signalling pathway behind macrophage inflammatory activity

Large genetic study suggests shared biological processes cause irritable bowel syndrome and anxiety

An international study of more than 50,000 people with irritable bowel syndrome (IBS) has revealed that IBS symptoms may be caused by the same biological processes as conditions such as anxiety. The research highlights the close relationship between brain and gut health and paves the way for development of new treatments.