Dr. Mark Sundrud, professor of medicine at the Geisel School of Medicine at Dartmouth College, sits down HCP live The interactions between bile acids and T cells, opportunities for applying this knowledge in clinical practice, and areas that may require further research are discussed.
Sundrud is a speaker at the “Enterohepatic Axis as a Therapeutic Target in Cholestatic Liver Disease” session at the American Association for the Study of Liver Diseases (AASLD) 2023 Liver Meeting in Boston this weekend, where he will speak about the liver -Intestinal axis and bile acid-induced intestinal T lymphocyte polarization.
As knowledge continues to emerge about the role of bile acids within and outside the liver, experts are showing increasing interest in understanding how T cells contribute to the pathogenesis of cholestatic liver disease and the broader link between gut and liver function. interest of.
“We’re starting to really understand that the liver and the gut are very closely connected. If there’s disease in the liver, that absolutely affects what’s going on in the gut. Likewise, if there’s pathophysiology in the gut, then it feeds back and changes the bile acids and the The way they return to the liver,” Sundrud said.
When it comes to understanding how bile acids affect T cells, Sundrud noted two important points to consider: the impact of bile acid toxicity on T cells, and the bile acid receptors expressed by T cells.
“Generally speaking, if you have high concentrations of bile acids, like many other cells, this is potentially dangerous for T cells. Lymphocytes in the liver and gut have found ways to compensate for high concentrations of potentially toxic bile acids. ” Sundrud explained. “The second thing that became clear is, of course, we now know that many immune cells express very specific bile acid receptors, and we and others have shown that there are at least some different types of nuclear receptors that are expressed in T cells . cells can be helped not only to respond to the presence of bile acids in general, but also to the presence of different types of bile acids.”
So far, research has focused on understanding how bile acids interact with liver cells, and the findings suggest that the most effective therapies in clinical studies of human liver disease affect both hepatocytes and intestinal cells. Efforts are now underway to understand which types of bile acids signal through which types of receptors in specific cells, with the goal of achieving the beneficial effects of bile acid derivatives in the liver and intestines.
“I think the idea that immune cells, particularly T cells, contribute to the pathogenesis of cholestatic liver disease is still emerging. We don’t understand how it works, and I think it’s time to say which drugs or which prospective drugs can take advantage of immune modulation It may be too early to achieve a therapeutic effect,” Sundrud said. “I just don’t know that the field is still there. Hopefully that’s why we continue to have these meetings, and then in 10 or 15 years, we can figure this out.”
Sundrud also emphasized the importance of considering gut and liver diseases from a broad physiological perspective and how they are connected and impact each other: “I think this will absolutely have an impact on our outcomes and how successfully we treat these diseases.”