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Receptor Plays Dual Role in Keeping Intestine's Immune System Balanced

Liang Zhou, MD, PhD, assistant professor of pathology and microbiology-immunology, is using an award from the Burroughs Wellcome Fund to study the aryl hydrocarbon receptor and its role in intestinal immunity.

New Northwestern Medicine® research has revealed one of the driving forces behind the regulation of immunity in the gut. Home to trillions of microorganisms, the intestines employ an army of “good bacteria” to fight infectious disease. The generals in charge of this defense system include innate lymphoid cells (ILCs), and their orders are in part given by a unique receptor. 

“Our lab has already published work showing that the aryl hydrocarbon receptor (Ahr) is important for the maintenance and function of ILCs and therefore immunity against pathogen infection, and we have now discovered that Ahr is important for the host to prevent autoimmune disease, too” said Liang Zhou, MD, PhD, assistant professor of pathology and microbiology-immunology. “If you do not have Ahr, you will have a defective immune response against infection and you may also be at risk for developing a disease where the body attacks itself.” 

The findings were published in Immunity

Committed to looking at the receptor from a variety of angles, including its effects on immune cell genes, Zhou is intrigued by the fact that the molecule that stimulates Ahr activity can be found within a normal diet, including a host of vegetables like broccoli, cauliflower, and cabbage. 

“We are trying to understand how the compounds in food activate Ahr because if we can figure that out, we will hold the potential to design new drugs,” said Zhou, also a Pew Scholar. “Our hope is to find a compound that can affect Ahr function, imploring those cells to combat pathogenic bacteria infections. If we can regulate Ahr activity, it will also allow us to prevent autoimmune diseases like colitis.” 

The links between infections, cancer, autoimmune diseases, and the environment are complex and mysterious, but a proper immune response is needed to fight illness. And yet, those same responses have to be kept from overreacting and attacking the body’s normal tissues. 

“Decoding the Ahr-mediated interactions among the gut’s resident bacteria, dietary components, and the immune system have broad and important biological implications,” said Zhou, a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “Because Ahr requires binding to small chemicals for its activity, varying those chemicals with drugs may eventually allow us to fine-tune the balance within the gut, thereby fighting infections or tumors while at the same time preventing autoimmunity.” 

Investigating Ahr is a new direction for Zhou’s lab and the work has been supported by the Burroughs Wellcome Fund. Named a 2013 Investigator in the Pathogenesis of Infectious Disease, Zhou was given a five-year $500,000 award from the foundation.

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