Breaking News
March 22, 2018 - HORIBA’s Microsemi CRP analyzer improves quality of care in emergency pediatric units, study shows
March 22, 2018 - Range of Vaginal Dryness Products Can Help Postmenopausal Women: Study
March 22, 2018 - Higher Dose Tx Deemed Safe in Pulmonary TB
March 22, 2018 - Diet soda associated with higher odds of diabetic retinopathy
March 22, 2018 - LSD reduces ‘sense of self’
March 22, 2018 - Vitamin D deficiency linked to metabolic syndrome in postmenopausal women
March 22, 2018 - Changes in the intestines may be responsible for reversal of diabetes after bariatric surgery
March 22, 2018 - iPads and Cancer; Clot Retrieval and Stroke: It’s PodMed Double T!
March 22, 2018 - Premature births linked to changes in mother’s bacteria
March 22, 2018 - Brain SPECT scans predict treatment outcomes in patients with depression
March 21, 2018 - Researchers succeed in integrating artificial organelles into cells of living organism
March 21, 2018 - Researchers discover ‘missing mutation’ in severe infant epilepsy
March 21, 2018 - Researchers develop statistics-based computational scheme to zoom in on brain function
March 21, 2018 - Verge joins Genomics England’s Discovery Forum industry partnership
March 21, 2018 - Trovagene Announces First Patient Successfully Completes Cycle 1 of Treatment with PCM-075 in Combination with Low Dose Cytarabine (LDAC) in AML Trial
March 21, 2018 - Congenital Cardiac Cath Tx Often Strays from Guidelines
March 21, 2018 - Marked increase in cardiovascular risk factors in women after preeclampsia
March 21, 2018 - New app may help predict, track manic and depressive episodes in bipolar patients
March 21, 2018 - Discovery of genes could lead to development of novel therapies for EBV-related cancers
March 21, 2018 - High-fat, high-cholesterol diet depletes ranks of artery-protecting immune cells
March 21, 2018 - Research misconduct allegations shadow likely CDC appointee
March 21, 2018 - Most Breast Ca Patients Fail to Get Genetic Counseling
March 21, 2018 - Lopsided ear function can lead to lopsided brain development
March 21, 2018 - Acupuncture helps manage menopausal symptoms, review finds
March 21, 2018 - Motor skill training may contribute to reading skills in obese children
March 21, 2018 - Poor dental health may be related to increased diabetes risk
March 21, 2018 - Chronic opioid users at increased risk of complications after spinal fusion surgery
March 21, 2018 - Study uncovers potential therapeutic target against large family of parasites
March 21, 2018 - NSAID use linked to increased risk of atrial fibrillation
March 21, 2018 - Scientists develop brain “stethoscope” that can detect silent seizures
March 21, 2018 - New method predicts effects of global warming on disease
March 21, 2018 - Insurance Company Hurdles Burden Doctors, May Harm Patients
March 21, 2018 - Renal Transplant from HCV-Positive Donors Feasible
March 21, 2018 - Myelodysplastic syndrome: MedlinePlus Medical Encyclopedia
March 21, 2018 - Research reveals brain mechanism involved in language learning
March 21, 2018 - Many parents still hesitate to try early peanut introduction, survey finds
March 21, 2018 - Audiologist urges tinnitus sufferers facing ‘revolving door healthcare’ to seek support
March 21, 2018 - Study reveals impact of prostate cancer on wives and partners of sufferers
March 21, 2018 - ‘Almost a Miracle Drug’: What We Heard This Week
March 21, 2018 - Study shows NIH spent >$100 billion on basic science for new medicines
March 21, 2018 - Columbia researchers identify nerve cells that drive fruit fly’s escape behavior
March 21, 2018 - Sartorius Stedim Biotech selected by ABL Europe to supply single-use process technologies
March 21, 2018 - Increase in coffee consumption may help battle against colon cancer
March 21, 2018 - Hydrogel may accelerate healing of diabetic ulcers
March 21, 2018 - Dermira’s Two Phase 3 Trials Evaluating Olumacostat Glasaretil in Patients with Acne Vulgaris Did Not Meet Co-Primary Endpoints
March 21, 2018 - DePuy Synthes introduces ACTIS Total Hip System for improving initial implant stability
March 21, 2018 - ‘Oh, It Was Nothing’
March 21, 2018 - Herbal drug kratom linked to salmonella illnesses, CDC says
March 21, 2018 - New optical point-of-care device could enhance screening for thyroid nodules
March 21, 2018 - FDA Expands Approval of Adcetris (brentuximab vedotin) for First-Line Treatment of Stage III or IV Classical Hodgkin Lymphoma in Combination with Chemotherapy
March 21, 2018 - Eosinophilic Esophagitis: Late Manifestation of Allergic March
March 21, 2018 - Signaling pathway involving the Golgi apparatus identified in cells with Huntington’s disease
March 21, 2018 - Quintupling inhaled steroid doses may not benefit children with asthma
March 21, 2018 - Study shows clear connection between cardiovascular fitness in middle age and dementia risk
March 21, 2018 - Premature babies have higher risks of health complications in Bangladesh
March 21, 2018 - Child’s temperament and parenting influence weight gain in babies
March 21, 2018 - Researchers find the heart to be capable of arrhythmia termination after local gene therapy
March 21, 2018 - Inhealthcare to provide digital infrastructure for NHS to help protect people from falls
March 21, 2018 - Flu Season Finally Slowing Down
March 21, 2018 - Mixed Results for Shorter DAPT in ACS Patients
March 21, 2018 - Scientists discover fish scale-derived collagen effective for healing wounds
March 21, 2018 - Genomics England announces new partnership to improve efficiency of next-generation sequencing analysis
March 21, 2018 - Adjuvant AC chemotherapy found to be effective in treating HRD-positive breast cancer patients
March 21, 2018 - Researchers identify new treatment targets for lung diseases using big data
March 21, 2018 - Kids see more women in science than five decades ago
March 21, 2018 - Research shows link between chronic fatigue syndrome and lower thyroid hormone levels
March 21, 2018 - Alzheimer’s disease on the rise
March 21, 2018 - Two Agents Equal as Pretreatment for Adrenal Tumor Surgery
March 21, 2018 - ‘Icebreaker’ protein opens genome for T cell development, researchers find
March 21, 2018 - Women in medicine shout #Metoo about sexual harassment at work
March 21, 2018 - Mother’s pre-pregnancy waist size may be linked to child’s autism risk
March 21, 2018 - Second hand marijuana smoke can cause serious damage
March 21, 2018 - International study shows benefits of using MRI at the start of prostate cancer diagnosis
March 20, 2018 - Santhera Reports Outcome of Exploratory Trial with Idebenone in PPMS Conducted at the NIH
March 20, 2018 - ECG Patch Ups At-Home Afib Diagnosis in mSToPS Trial
March 20, 2018 - ROS-scavenging nanozymes for anti-inflammation therapeutics
March 20, 2018 - Genomics England announces appointment of global genomics pioneer as first CEO
March 20, 2018 - Test flight at German Aerospace Center in Cologne demonstrates functionality of deficopter
March 20, 2018 - Music therapy helps treat combat-related psychological injuries in military personnel
March 20, 2018 - Innovative psychotherapeutic treatment protocol for obsessive-compulsive disorders
Dysfunctional gene may be cause of Crohn’s disease in some patients

Dysfunctional gene may be cause of Crohn’s disease in some patients

image_pdfDownload PDFimage_print

This holiday season, millions of people will gather at airports ready to board planes for destinations around the world. Depending on the environment at their destination, their suitcases may be filled with sunscreen and bathing suits, or heavy parkas and mittens.‘,sans-serif;”>

Now, a new study from the lab of biologist Mark Sundrud, Ph.D., on the Florida campus of The Scripps Research Institute (TSRI), provides evidence that circulating immune cells may similarly adapt when they enter different tissues, which are like different environments in our bodies. Moreover, the researchers found that inability to adapt may lead to disease.‘,sans-serif;”>

The scientists hope understanding how immune cells adapt as they enter different tissues will spur the design of better, more specific, medicines.‘,sans-serif;”>

“We need therapeutic strategies that specifically target chronic inflammation in the gut, skin or other tissues,” Sundrud says, “instead of just generally suppressing the entire immune system.”‘,sans-serif;”>

The research was published Dec. 19, 2017, in the journal Immunity‘,sans-serif;”>.‘,sans-serif;”>

Sundrud’s laboratory is working to understand the characteristics and functions of TH17 cells, a subset of immune cells that circulate throughout the body. These cells protect many types of tissues from infection, but they can also promote chronic inflammatory conditions like Crohn’s disease, which specifically targets the intestinal tract.

Knowing TH17 cells need to function in a variety of tissue environments throughout the body, Sundrud’s team wondered if and how these cells might use different tools to behave normally in one environment-;or tissue-;than they’d use in another. Perhaps activating one gene could be useful in the lungs, while activating another would be useful in the gut, the same way you might bring a bathing suit on a trip to Florida and a jacket if you’re headed to Canada.

This study built on previous research from the Sundrud lab, which showed that when TH17 cells entered the intestine in human tissue samples, they increased the expression of a gene called MDR1.

But MDR1 is only known to transport chemotherapeutic drugs out of tumor cells, so why would it be expressed in immune cells in the gut?

The new study suggests that MDR1 is responsible for protecting TH17 cells in the gut from bile acids-;detergent-like molecules produced by the liver that break down fats. Normally, the liver secretes bile acids after we eat to aid digestion. As food moves through the digestive tract, these acids are reabsorbed when they reach the ileum-;the final portion of the small intestine-;and the site of ileal Crohn’s disease, the most common form of Crohn’s.

“T cells only see high levels of bile acids in the ileum. They know this, and they adapt once they get there,” says Sundrud.

This discovery led the researchers to identify a mechanism where ileal Crohn’s disease appears to be induced by bile acids when T cell adaptation does not occur the way it should.

The team used a genetically modified mouse model to observe the expression and function of MDR1 in mice. They found that the gene’s expression increased when the cells entered the ileum. But, in mice where the gene couldn’t be activated in the gut, TH17 cells that were exposed to bile acids suffered severe oxidative stress. This stress caused the TH17 cells to become overactive, leading to Crohn’s disease-like intestinal inflammation in mice.

Using bile acid sequestrants, an FDA-approved class of drugs used in transplant patients that absorb bile acids like a sponge, scientists were able to restore normal T cell function in the ileum and attenuate Crohn’s disease in mice.

To establish the relevance of their findings, the team tested blood samples from healthy humans, as well as those with a variety of inflammatory bowel diseases, including Crohn’s. They found a subset of patients with ileal Crohn’s disease had severely impaired MDR1 expression.

Not only does this suggest that the cause of Crohn’s disease in these patients may be oxidative stress due to dysfunctional MDR1, but that for the subset of patients with this dysfunction, bile acid sequestrants may be an effective treatment. Together with his collaborators, Sundrud hopes to fund a clinical study to test exactly that.​


Tagged with:

About author

Related Articles