The Body’s Trash Disposal System

May 14, 2018

Professor Tracy McGaha, courtesy Princess Margaret Cancer Foundation, UHNProfessor Tracy McGaha Just like a large city, the body has a several systems in place to dispose of different types of waste. And when one of these systems malfunctions, serious problems can arise.

Tracy McGaha, an associate professor of immunology at the University of Toronto and a senior scientist at the Princess Margaret Cancer Centre, has shown that disrupting efferocytosis — the process through which dead cells are removed from the body — promotes the development of lupus. The findings of the study were published today in the prestigious journal Nature Immunology.

Lupus occurs when the immune system mistakenly attacks healthy tissues throughout the body, including those of the joints, skin, kidneys, blood, heart and lungs. The abnormal immune response can cause significant inflammation and damage to these parts of the body. 

The cause of lupus and the immune mechanisms responsible for its damage remain elusive. This gap in knowledge has precluded the development of effective treatments that target the underlying cause of the disease.

“The link between lupus and efferocytosis is that they both involve the immune system,” explains McGaha. “In efferocytosis, specialized immune cells known as phagocytes seek out dead cells, then engulf and digest them—acting like the body’s trash collectors.”

The researchers showed that when phagocytes ‘eat’ dead cells, the immune system is suppressed through the action of a protein known as the aryl hydrocarbon receptor (AhR). In contrast, when phagocytes lacking AhR eat dead cells, the immune system is not suppressed and the body attacks healthy tissues, causing damage similar to that seen in lupus.

Dr. McGaha’s team also found that AhR activity can affect disease severity in an experimental model of lupus: disease symptoms worsen when AhR is inhibited, whereas disease symptoms improve when AhR is activated.

Dr. McGaha comments, “the results of our study suggest that AhR activity is a key mechanism that prevents the immune system from attacking normal tissues. We believe that this new knowledge could be exploited to not only develop new more effective treatments for lupus, but also to make the immune system better at destroying cells that have become cancerous.”

The research was supported by the National Institutes of Health, the Canada First Research Excellence Fund, the Swedish Medical Research Council, the Karolinska Institute (Sweden), the Canada Foundation for Innovation and The Princess Margaret Cancer Foundation. Research collaborator Daniel De Carvalho holds a Tier 2 Canada Research Chair in Cancer Epigenetics and Epigenetic Therapy.

This story is based on a media release from by Strategic Research Initiatives Development (StRIDe), University Health Network.

Journal article author list: Shinde R, Hezaveh K, Halaby MJ, Kloetgen A, Charkravarthy A, da Silva Medina T, Deol R, Manion KP, Baglaenko Y, Eldh M, Lamorte S, Wallace D, Chodisetti SB, Ravishankar B, Lui H, Chaudary K, Munn DH, Tsirigos A, Madaio M, Grabrielsson S, Touma Z, Wither J, De Carvalho D, McGaha TL. 

May
24 – 26
Indigenous Health Conference
Conference | 7:00am–5:30pm
May 25 GTA Rehab Network’s Best Practices Day 2018
Conference | 8:00am–4:00pm
May 30 Making Workplace-Based Assessment Work for Trainees, Supervisors and Training Programs
Workshop/Seminar | 1:00pm–4:00pm
May 31 The Brian D Hodges Symposium
Symposium | 8:00am–2:00pm
Jun 1 Real Impact: Strengthening SLP Community through Collaboration
Symposium | 8:30am–4:30pm
Jun
1 – 2
Alumni Reunion
Other | 6:00pm–6:00pm
Jun 1 Alumni Reunion - Dean's Reception & Alumni Awards
Reception | 6:00pm–9:00pm

Tweets

UofT Medicine
@uoftmedicine
RT : Daydreaming may help you become more socially adept https://t.co/iwUKfB3GjO https://t.co/3e6KPoz9va
UofT Medicine
@uoftmedicine
“We need to strengthen our structures and processes within the Faculty of Medicine to ensure everyone feels safe, s… https://t.co/jw6aMqi2fK
UofT Medicine
@uoftmedicine
Global Health Day 2018 will bring together experienced experts in activism and global health with new doctors and m… https://t.co/TSIGXTJYU0

UofTMed Magazine

The Humour issue. Is laughter really the best medicine?

Sign up for your free digital copy.
Back to Top