Crohn's disease may develop from warped immune cell signaling during bile acid exposure Study reveals how T cells in the small intestine respond to bile acids, offering localized treatment direction for a cause of chronic illness.
April 07, 2021
JUPITER, FL People with Crohn's disease are typically treated with powerful anti-inflammatory medications that act throughout their body, not just in their digestive tract, creating the potential for unintended, and often serious, side effects. New research from the lab of Mark Sundrud, PhD, at Scripps Research, Florida suggests a more targeted treatment approach is possible.
Crohn's disease develops from chronic inflammation in the digestive tract, often the small intestine. More than half a million people in the United States live with the disease, which can be debilitating and require repetitive surgeries to remove irreversibly damaged intestinal tissue.
Writing in the journal Nature, Sundrud's team finds that certain immune cells in the small intestine have evolved a molecular sensing mechanism to protect themselves from the toxic effects of high bile acid concentrations in the small intestine. This sensory mechanism can be manipulated with small drug-like molecules, they find, and the treatment reduced small bowel inflammation in mice.
It seems that these immune cells, called T effector cells, have learned how to protect themselves from bile acids, Sundrud says. These T cells utilize an entire network of genes to interact safely with bile acids in the small intestine. This pathway may malfunction in at least some individuals with Crohn's disease.
Bile acids are made in the liver and released during a meal to help with digestion and absorption of fats and fat-soluble vitamins. They are actively recaptured at the end of the small intestine, in an area called the ileum, where they pass through layers of tissue that contain the body's dense network of intestinal immune cells, and ultimately re-enter the blood stream for return to the liver.
Because they are detergents, bile acids can cause toxicity and inflammation if the system becomes unbalanced. The whole process is kept humming along thanks to an intricate signaling system. Receptors in the nucleus of both liver cells and intestinal barrier cells sense the presence of bile acid and tell the liver to back off on bile acid production if there's too much, or to produce more if there aren't enough to digest a big steak dinner, for example.
Given how damaging bile acids can potentially be to cells, scientists have wondered how immune cells that live in or visit the small intestine tolerate their presence at all. Sundrud's team previously reported that a gene called MDR1, also known as ABCB1, becomes activated when an important subset of immune cells that circulate in blood, called CD4+ T cells, make their way into the small intestine. There, MDR1 acts in transitory T cells to suppress bile acid toxicity and small bowel inflammation.
In the new study, Sundrud's team uses an advanced genetic screening approach to uncover how T cells sense and respond to bile acids in the small intestine to increase MDR1 activity.
The basic discovery that T cells dedicate so much of their time and energy to preventing bile acid-driven stress and inflammation highlights completely new concepts in how we think about and treat Crohn's disease, Sundrud says. It's like we've been digging in the wrong spot for treasure, and this work gives us a new map showing where X marks the spot.
The T cells contain a receptor molecule in their nucleus known as CAR, short for constitutive androstane receptor. Acting in the small intestine, CAR promotes expression of MDR1, and also plays a role in activating an essential anti-inflammatory gene, IL-10, the team found.
When we treated mice with drug-like small molecules that activate CAR, the result was localized detoxification of bile acids and reduction of inflammation, Sundrud says.
Sundrud says exploring the therapeutic potential of CAR activation will require caution and creativity, because CAR is also critical for breaking down and eliminating other substances in the liver, including many medicines.
Ultimately, the Crohn's disease therapy that emerges from this work could be something that activates CAR locally in small intestinal T cells, or something that targets another gene that is similarly responsible for promoting the safe communication between small intestinal T cells and bile acids, Sundrud says.
Also interesting, the team found that the bile acid-inflammation feedback system worked somewhat differently in the colon in concert with gut microbiome factors. While gut flora had more influence on T cell development and function in the colon, it was the nuclear receptor CAR that had more influence on inflammation in the small intestine.
Inflammation plays both positive and negative roles in the body. It can damage tissue, but it also suppresses cancer growth and fights infections. The current anti-inflammatory treatments shut it down systemically, throughout the entire body. That can have potentially serious consequences, such as lowering resistance to infections or easing off the brake on cancer. Directing treatment for inflammatory diseases only to the affected tissue would be preferable whenever feasible, he says.
The roughly 50 million people living in the US with some sort of autoimmune or chronic inflammatory disease are all treated the same, medically, Sundrud says. The holy grail would be to come up with druggable approaches to treat inflammation in only specific tissues and leave the rest of the immune cells in your body untouched, and able to fend of cancer and microbial infections.
In addition to lead author Mark Sundrud, the authors of the study, CAR directs T cell adaptation
Europe Stories
06/10/2025
France T l visions, France's leading broadcaster, has received the 2025 EBU ...
04/09/2025
Monumental Sports & Entertainment (MSE), in collaboration with Dalet, has been a...
07/08/2025
July 8 2025, 22:30 (PDT) Tata Motors & Dolby Bring Dolby Atmos to Harrier.ev, R...
11/07/2025
If you've ever wondered what might be playing in Clark Kent's headphones...
11/07/2025
AI and Multimedia Authenticity Standards Collaboration launches two papers to guide the future of AI integration, today at the AI for Good Global Summit
The...
10/07/2025
The current holder of the prestigious Thomson Foundation Young Journalist of the Year Award has been forced to stop reporting over fears for her safety in Afgha...
10/07/2025
Spotify is turning up the volume on Australian music with a multipronged initiative designed to highlight the dominance of Australian artists on the global stag...
10/07/2025
This is not a drill: Oasis is back on the road-marking its first live performanc...
10/07/2025
The music industry depends on fresh ideas, bold voices, and emerging talent. Yet across the U.K., too many young musicians lack the space to develop their craft...
10/07/2025
10 Jul 2025
VEON and Cohen Circle Secure Investor Commitments for Kyivstar Listing Kyiv, New York, Dubai, and Philadelphia - July 10, 2025 - VEON Ltd. (Nasdaq:...
10/07/2025
Thursday 10 July 2025
The Very Small Creatures
Jaime's Treetop Tales
Emerald
BooSnoo! Christmas Mashup
Pip & Posy's Spooktacular Party
The Very Sm...
10/07/2025
Thursday 10 July 2025
Brand new rewards are coming to Sky customers, with free ...
10/07/2025
Comscore Achieves Full JIC Certification for National TV Measurement Including...
09/07/2025
Wednesday 9 July 2025
Sky Broadband now has the UK's fastest broadband spee...
09/07/2025
CUPERTINO, CALIFORNIA Apple today announced Jeff Williams will transition his role as chief operating officer later this month to Sabih Khan, Apple's senior...
08/07/2025
In an era where digital threats to journalists are becoming increasingly aggressive and widespread, MediaSafe Africa launches as a vital online resource to help...
08/07/2025
This summer, as the energy builds for one of the biggest moments in women's ...
08/07/2025
UKTV today announces that Richard Watsham, Chief Creative Officer at UKTV and Global Director of Acquisitions for BBC Studios/UKTV, has decided to step down fro...
08/07/2025
SAN JOSE, Calif. - July 8, 2025 - Harmonic (NASDAQ: HLIT) today announced a reco...
08/07/2025
Arvato Systems Optimizes Customer Communication with AOK Niedersachsen
New project in the statutory health insurance sector
Arvato Systems and AOK Niedersach...
08/07/2025
On August 7, Apple Arcade is adding four exclusive games to its diverse catalogue of more than 200 fun games for players to enjoy, all free from ads and in-app ...
07/07/2025
** MEDIA ALERT **
VIZ Media Ignites AX 2025 with Star-Studded Panels, Exclus...
07/07/2025
CULVER CITY, CALIFORNIA As Apple Music marks its 10th anniversary this year, Apple unveils its most ambitious creative project to date: a brand-new state-of-the...
07/07/2025
RT has announced that Mark Bignell has been appointed Commissioning Editor for Comedy following a public competition. This senior editorial position will drive...
04/07/2025
The Summer Reading Challenge has inspired children across the U.K. to embrace a ...
04/07/2025
Friday 4 July 2025
Watch the trailer here https://youtu.be/Od5WpvWmDr8
Further...
04/07/2025
The Pitch comes to RT Radio 1 airwaves this Sunday at 7pm. The Pitch is a brand...
03/07/2025
For our Vario-Jib, as well as for a repertoire of weights, we now have carts that make transport easier...
03/07/2025
One of our latest innovations: Slider Drive Unit!
Our Vario Slider not only comes with improvements and new features, but also with its own drive unit!
Our i...
03/07/2025
The 360 EVO lives up to its name: 360-degree rotation not only on the pan axis, but also on the roll axis, enables filmmakers to take their creative visions eve...
03/07/2025
What a buzzing few days at BSCExpo in London!
We were thrilled to connect with so many talented professionals from the world of cinematography.
A huge thank ...
03/07/2025
ADOLESCENCE - Shot with Panther Tower"The whole rig had to be detachable mid-episode
Netflix limited drama series Adolescence has been gaining attentio...
03/07/2025
** MEDIA ALERT ** Shonen Jump Store Hosting Los Angeles Pop-up During Anime Exp...
03/07/2025
Thursday 3 July 2025
David Harewood and Matthew Broome in Mozart: Genius for Hi...
03/07/2025
The Sky WNT Fund supports Womens National Team players with a 30,000 bursaryThursday 3 July 2025
Sky Ireland has announced the four recipients of the 2025 Sky...
02/07/2025
Calrec expands ecosystem at NAB 2025 giving broadcasters access to dynamic workflows and ultimate flexibility Helping broadcasters meet the shifting needs of me...
02/07/2025
02 Jul 2025
VEON Raises USD 200 Million in Private Bond Placement Dubai, July 1, 2025: VEON Ltd. (Nasdaq: VEON), a global digital operator ( VEON ), announces ...
02/07/2025
Brand new factual series follows mechanic and self-taught engineer Dom Chinea as he makes the move of his life to the far west of Cornwall
UKTV today announces...
02/07/2025
Rohde & Schwarz acquires ZES ZIMMER Electronic Systems GmbH and expands its T&M ...
02/07/2025
Wuppertal July 2, 2025
Riedel Communications Launches RefSuite Ecosystem for S...
02/07/2025
Andrew will serve as Chair of ABC alongside his role at NED, APL Media, where he supports the executive team with strategic insight and global expansion plans. ...
01/07/2025
The launch of Code of Silence, coupled with the Britains Got Talent semi final, gave ITV its best Sunday night of 2025.
The first episode of the new crime dr...
01/07/2025
ITV and Mammoth Screen have announced the start of filming for Betrayal, a gripp...
01/07/2025
eds3_5_jq(document).ready(function($) { $(#eds_sliderM519).chameleonSlider_2_1({ content_source:......
01/07/2025
Vocal-processing plug-in joins NOIZ Hub series
Launched in 2024, KIT Plugins' NOIZ Hub series was created with the aim of providing a range of professio...
01/07/2025
New self-paced learning programme announced
Mastering.com have announced the availability of a new online course designed to cover the fundamentals of maste...
01/07/2025
The Traitors are coming: Get your first taste of the global hit as Season 1 of T...
01/07/2025
cetecom advanced certifies Rohde & Schwarz test solution for the verification of...
01/07/2025
RT has announced that Teresa Smith has been appointed Commissioning Editor with responsibility for Factual Entertainment following a public competition. This s...
Crohn's disease may develop from warped immune cell signaling during bile acid exposure Study reveals how T cells in the small intestine respond to bile acids, offering localized treatment direction for a cause of chronic illness.
