Breaking News
April 20, 2018 - Long-term exposure to cold temperatures reduces diabetes and obesity, shows study
April 20, 2018 - Metabolic Syndrome Common With Chronic Hep B Infection
April 20, 2018 - Tracking quality of life during prostate cancer treatment
April 20, 2018 - Study shows presence of beta-amyloid dimers in the brains of Alzheimer’s patients
April 20, 2018 - Researchers identify link between physical inactivity and increased risk of dying from cancer
April 20, 2018 - Breathtaking evolution amongst Indonesian tribe
April 20, 2018 - Study shows testosterone deficiency in men is associated with chronic diseases
April 20, 2018 - Simple one-page form helps improve satisfaction of patients with care
April 20, 2018 - Researchers evaluate accuracy of simple blood test to predict lung cancer
April 20, 2018 - Study looks at sperm producing ability in testicular cancer patients
April 20, 2018 - Exercise In, Vitamin D Out for Preventing Falls: U.S. Panel
April 20, 2018 - Skin cancers associated with decreased risk of developing AD
April 20, 2018 - Preserving fertility during chemotherapy
April 20, 2018 - Teva and Procter & Gamble Company terminate PGT Healthcare partnership
April 20, 2018 - People diagnosed with traumatic brain injury may have increased risk of Parkinson’s disease, shows study
April 20, 2018 - Researchers use smartphone to diagnose people infected with Loa loa worm
April 20, 2018 - College students with autism have high rate of suicidal thoughts
April 20, 2018 - Study sheds light on how the HSC niche is maintained
April 20, 2018 - Drug test spurs frank talk between hypertension patients and doctors
April 19, 2018 - Low-cost deworming drug improves female farmers’ physical fitness
April 19, 2018 - Genome editing identifies neural circuit behind leptin’s anti-obesity and anti-diabetes effects
April 19, 2018 - Many European countries lack comprehensive policy to eliminate viral hepatitis
April 19, 2018 - Young people with ADHD ‘more likely’ to come from deprived neighbourhoods
April 19, 2018 - SLU professor discovers new biomarkers for chlorine gas exposure
April 19, 2018 - Study proposes new mechanism that may contribute to gender differences in weight control
April 19, 2018 - Sleep restriction therapy does not interfere with insomnia patient’s driving ability, research shows
April 19, 2018 - Deep brain stimulation offers relief to UTHealth patient with treatment-resistant depression
April 19, 2018 - Study shows fatty fish and camelina oil boost HDL and IDL cholesterol
April 19, 2018 - FDA Alert: Euphoric Capsules by Epic Products: Recall
April 19, 2018 - Researchers identify peptide produced during cartilage deterioration as a potential source of osteoarthritis pain
April 19, 2018 - New breakthrough may allow scientists to orchestrate tissue regeneration in humans
April 19, 2018 - SYGNIS AG introduces new TruePrime apoptotic cell free DNA amplification kit
April 19, 2018 - Innovative device shows promise in capturing and releasing circulating tumor cells
April 19, 2018 - Researchers shed light on role of striosomal neurons in reinforcement learning
April 19, 2018 - Genetic make-up impacts long-term effectiveness of phobia treatment
April 19, 2018 - Novel biomarker can distinguish malignant lung nodules
April 19, 2018 - Study reports promising novel approach to treat therapy resistant pediatric brain tumors
April 19, 2018 - One-Hour Plasma Glucose Useful Predictor of Diabetic Retinopathy
April 19, 2018 - Hydroxychloroquine no more effective than placebo for relieving osteoarthritis hand pain
April 19, 2018 - Transplanted livers have a protective effect and reduce potential for organ rejection
April 19, 2018 - Researchers develop new method to study activity of inflammatory cells
April 19, 2018 - Researchers discover highly antibiotic resistant superbugs in Gulf States
April 19, 2018 - Smart-tooth technology shows promise in detecting certain diseases in high-risk patients
April 19, 2018 - Interaction between dioxin and HLA gene variant activates events associated with rheumatoid arthritis
April 19, 2018 - Eyes of adolescents could be associated with increased risk of cardiovascular disease in later life
April 19, 2018 - U.S. Women Less Likely Than Men to Get Statins After Heart Attack
April 19, 2018 - Health Canada grants cannabis cultivation license to High Park Farms
April 19, 2018 - Atypical brain development observed in preschoolers with ADHD symptoms
April 19, 2018 - SC Johnson releases annual Sustainability Report
April 19, 2018 - Positive attitudes about aging reduce risk of dementia in older adults
April 19, 2018 - Environmental pollutants found to worsen rheumatoid arthritis
April 19, 2018 - UT Southwestern scientists discover protein linked to metastatic breast cancer
April 19, 2018 - Study highlights need for further evidence to improve symptom management in end of life care
April 19, 2018 - Detecting diminished dopamine-firing cells inside brain could reveal earliest signs of Alzheimer’s
April 19, 2018 - Uniqsis offers high-power LED light unit for scalable flow photochemistry reactions
April 19, 2018 - Case study shows how intravascular ultrasound imaging helps detect acute aortic syndrome
April 19, 2018 - Research reveals new mechanism by which HIV evades the immune system
April 19, 2018 - Nanodisc-delivered cancer treatment helps eliminate tumors
April 19, 2018 - Functional connectivity MRI could help detect brain disorders and diseases
April 19, 2018 - Finding better way to quantify neuropathy symptoms and treatment efficacy
April 19, 2018 - Study examines effectiveness of caregiver education about sickle cell trait
April 19, 2018 - High-resolution images of tumor vasculature using new technology
April 19, 2018 - Lack of sleep may be linked to risk factor for Alzheimer’s disease
April 19, 2018 - Study finds neurotransmitter may play a role in alcohol relapse, addiction
April 19, 2018 - Researchers build molecular networks of calcific aortic valve disease
April 19, 2018 - Researchers develop highly specific apoptosis assay for pharmacodynamic analyses of tumor specimens
April 19, 2018 - Scientists decipher mechanism of chemotherapy induced female infertility
April 19, 2018 - New insight may allow researchers to design drugs that improve immune responses to vaccines
April 19, 2018 - FDA Approves Crysvita (burosumab-twza) for X-Linked Hypophosphatemia
April 19, 2018 - Researchers uncover origin of virus-fighting plasma B cells
April 19, 2018 - Study finds no evidence of lower intelligence in young children who had anesthesia
April 19, 2018 - Baboons break out of research facility briefly
April 19, 2018 - Study shows how deployment time increases risk of suicide attempt in soldiers
April 19, 2018 - Specific odors from malaria infected individuals attract more mosquitoes
April 19, 2018 - FDA Alert: Rhino 69 Extreme 50000 by AMA Wholesale: Recall
April 19, 2018 - Top HIV cure research team refutes major recent results on how to identify HIV persistence
April 19, 2018 - Experts propose new solutions to increase benefit, affordability of targeted cancer medicines
April 19, 2018 - Deficiency of innate immune adaptor TRIF shortens survival time of ALS mice
April 19, 2018 - New machine learning method offers better way to detect heart disease
April 19, 2018 - CNIO researchers determine structure of protein complex related to cell survival
International researchers find valuable clues for developing robust therapeutic agents against IBDs

International researchers find valuable clues for developing robust therapeutic agents against IBDs

image_pdfDownload PDFimage_print

International researchers show CD4+ T effector cells express xenobiotic transporter Mdr1 in the presence of bile acids to maintain homeostasis in the small intestine

Our immune system protects our bodies from numerous pathogenic microbes and toxins in the environment. The system comprises innate (non-specific) and adaptive (acquired) immunity. When innate immune cells recognize pathogens, the adaptive immune system is called into action. There are two types of adaptive immune responses: humoral immunity mediated by antibodies produced by B cells, and cell-mediated immunity mediated by T cells, a type of white blood cells.

CD4+ T cells regulate/suppress immune responses through several mechanisms.”naïve” CD4 T cells can differentiate into one of several lineages of effector (Teff) cells, including Th1 and Th17. In disease-free state, Teff cells are tightly regulated by intestinal microbiota, which is the community of microorganisms that normally inhabits the digestive tracts of humans and other animals. However, when there is an accumulation of Th17 and Th1 cells in the intestine, the symbiotic relationship may be disrupted, leading to conditions such as inflammatory bowel diseases (IBDs), a group of debilitating and sometimes leads to life-threatening conditions that affect the colon and small intestine.

While a great deal is known about the mechanisms underlying the symbiotic interactions between Teff cells and intestinal microbiota, far less is known about the interaction of Teff cells with metabolites, which are the intermediates and products of metabolism. This motivated an international team of researchers centered at Japan’s Osaka University to fill the knowledge gap, potentially yielding valuable clues for development of robust therapeutic agents against IBDs.

For their study, the researchers focused on bile acid, a detergent-like metabolite produced by the catabolism of cholesterol catabolism in the liver and deposited through the bile duct into the small intestine in response to food intake. Bile acids have been reported to induce oxidative stress in liver and epithelial cells by perturbing normal cell membrane architecture.

“We observed in mice that Teff cells upregulate the protein Mdr1, in the end portion of the small intestine (ileum) to maintain homeostasis in the presence of bile acids,” says Hisako Kayama, from Osaka University and author of the study recently published in Immunity. “Notably, those lacking Mdr1 display mucosal dysfunction and induce Crohn’s disease-like ileitis.”

Mdr1 is an important protein that is extensively distributed and expressed in the intestinal cells. It pumps xenobiotics (such as toxins or drugs) out of the cell, and has essential functions in Teff cells during bile acids exposure, limiting oxidative stress, promoting survival, and suppressing inflammatory cytokine expression. The team noted the inhibition of bile acids reabsorption in the ileum restores mucosal homeostasis in mice transplanted with Mdr1-deficient Teff cells, which underscores the involvement of Teff dysregulation in the pathogenesis of IBD.

“We have also successfully identified a discernable subset of ileal Crohn’s disease patients who display marked MDR1 loss-of-function in the presence of bile acids,” Kayama adds. “As such, future validation studies of larger IBD patient cohorts is important to test whether an Mdr 1 loss-of-function is associated with a unique clinical course of ileal CD. Such knowledge may present opportunities for non-traditional, bile acids-directed therapy.”

Source:

http://resou.osaka-u.ac.jp/en/research/2017/20171220_1

Tagged with:

About author

Related Articles