Breaking News
December 13, 2018 - Research findings could lead to new targets for cancer-fighting therapeutics
December 13, 2018 - Butantan Institute signs collaboration agreement with MSD to develop dengue vaccines
December 13, 2018 - Study explores how patients want to discuss symptoms with doctors
December 13, 2018 - RUDN medics first to gather scattered data on hepatitis morbidity in Somalia
December 13, 2018 - Age and gender disparities found in use of bed nets to prevent malaria in sub-Saharan Africa
December 13, 2018 - Caffeine therapy benefits developing brains of premature babies
December 13, 2018 - New review focuses on electrospinning techniques used in musculoskeletal tissue engineering
December 13, 2018 - A new division focused on human immune system
December 13, 2018 - Zogenix Announces Positive Phase 3 Trial Results on the Efficacy and Safety of Fintepla (ZX008) in Dravet Syndrome
December 13, 2018 - BCR ABL Genetic Test: MedlinePlus Lab Test Information
December 13, 2018 - Caffeinated beverages during pregnancy linked to lower birth weight babies
December 13, 2018 - Stanford Medicine Health Trends Report examines opportunity to democratize health care
December 13, 2018 - Obsessive-compulsive disorder may protect individuals from obesity
December 13, 2018 - Scientists investigate how a painful event is processed in the brain
December 13, 2018 - Genetic study reveals new insights into underlying causes of moderate-to-severe asthma
December 13, 2018 - Vitamin C supplementation for pregnant smokers may reduce harm to infants’ lungs
December 13, 2018 - New study reveals yin-yang personality of dopamine
December 13, 2018 - Children with high levels of callous traits show widespread differences in brain structure
December 13, 2018 - Long-term Benefit of Steroid Injections for Knee Osteoarthritis Challenged
December 13, 2018 - Adding new channels to the brain remote control
December 13, 2018 - In the Spotlight: A different side of neuroscience
December 13, 2018 - Medical Marvels: Using immunotherapy for melanoma that spread to the brain
December 13, 2018 - Puzzles do not keep dementia away finds study
December 13, 2018 - New mouse model shows potential for rapid identification of promising muscular dystrophy therapies
December 13, 2018 - Study reveals urban and rural differences in prenatal exposure to essential and toxic elements
December 13, 2018 - New collaborative partnership in quest of novel antibiotics
December 13, 2018 - Single tau molecule holds clues to help diagnose neurodegeneration in its earliest stages
December 13, 2018 - AHA Scientific Statement: Low Risk of Side Effects for Statins
December 13, 2018 - What Is Acute Flaccid Myelitis?
December 13, 2018 - How bereaved people control their thoughts without knowing it
December 13, 2018 - Health care democratization underway, according to 2nd annual Stanford Medicine Health Trends Report | News Center
December 13, 2018 - Going Beyond a Single Color
December 13, 2018 - London-based startup launches ‘thedrug.store’ aiming to clean up CBD industry
December 13, 2018 - Loss of tight junction barrier protein results in gastric cancer development
December 13, 2018 - Novel way to efficiently deliver anti-parasitic medicines
December 13, 2018 - RKI publishes new data on disease prevention and utilization of medical services
December 13, 2018 - High-tech, flexible patches sewn into clothes could help to stay warm
December 13, 2018 - The CCA releases three reports on requests for medical assistance in dying
December 13, 2018 - Restoring Hair Growth on Scarred Skin? Mouse Study Could Show the Way
December 13, 2018 - Probiotic use may reduce antibiotic prescriptions, researchers say
December 13, 2018 - Drug repositioning strategy identifies potential new treatments for epilepsy
December 13, 2018 - Chronic rhinitis associated with hospital readmissions for asthma and COPD patients
December 13, 2018 - Food poisoning discovery could save lives
December 13, 2018 - Cloned antibodies show potential to treat, diagnose life-threatening fungal infections
December 13, 2018 - Exercise may reduce colorectal cancer risk after weight loss
December 13, 2018 - Russian scientists create hardware-information system for brain disorders treatment
December 13, 2018 - Moderate alcohol consumption linked with lower risk of hospitalization
December 13, 2018 - Nurturing Healthy Neighborhoods | NIH News in Health
December 13, 2018 - Rise in meth and opioid use during pregnancy
December 13, 2018 - Researchers gain new insights into pediatric tumors
December 13, 2018 - FSU study finds racial disparity among adolescents receiving flu vaccine
December 13, 2018 - Study investigates attitudes toward implementation of ‘sex as a biological variable’ policy
December 13, 2018 - Drug cocktail induces cancer cell death by switching off energy supply
December 13, 2018 - Baculovirus virion completely eliminates liver-stage parasites in mouse model
December 13, 2018 - Researchers create noninvasive technology that detects when nerve cells fire
December 13, 2018 - Allen Institute for Immunology to partner with CU Anschutz to understand dynamics of human immune system
December 13, 2018 - Inability to do daily living tasks delays discharge of mental health patients
December 13, 2018 - Treating patients with hypertension induced albuminuria
December 13, 2018 - New substance could improve efficacy of established breast cancer treatments
December 13, 2018 - Scientists develop new stem cell line to study conversion of stem cells into muscle
December 13, 2018 - Re-programming the body’s energy pathway boosts kidney self-repair
December 13, 2018 - Research findings could help improve treatment of anxiety and post-traumatic stress disorders
December 13, 2018 - The Microbiome Movement announce Microbiotica as official industry partner
December 13, 2018 - New study reveals potential benefits of cEEG monitoring for infant ICU patients
December 13, 2018 - Whole-body imaging PET/MRI offers information to guide treatment options for prostate cancer
December 13, 2018 - International investigators fight against the negative campaign on benzodiazepines
December 13, 2018 - Targeting biochemical pathway may lead to new therapies for alleviating symptoms of anxiety disorders
December 13, 2018 - FDA Approves Tolsura (SUBA®-itraconazole capsules) for the Treatment of Certain Fungal Infections
December 13, 2018 - Are scientists studying the wrong kind of mice?
December 13, 2018 - Computer memory: A scientific team builds a virtual model of a key brain region
December 13, 2018 - Visual inspection alone is insufficient to diagnose skin cancer
December 13, 2018 - Paternal grandfather’s access to food associated with grandson’s mortality risk
December 13, 2018 - Our brain senses angry voices in a flash, study shows
December 13, 2018 - PM2.5 Exposure Linked to Asthma Rescue Medication Use
December 13, 2018 - Can’t exercise? A hot bath may help improve inflammation, metabolism, study suggests
December 13, 2018 - Can artificial intelligence help doctors with the human side of medicine?
December 13, 2018 - Virginia Tech and UC San Diego researchers team up to develop nonopioid drug for chronic pain
December 13, 2018 - NIH offers support for HIV care and prevention research in the southern United States
December 12, 2018 - Activating brain region could revive the urge to socialize among opioid addicts
December 12, 2018 - Relationship impairment appears to interfere with seeking mental health treatment in men
New study solves longstanding mystery in innate immunity

New study solves longstanding mystery in innate immunity

image_pdfDownload PDFimage_print

UT Southwestern biochemist and Breakthrough Prize winner Dr. Zhijian “James” Chen’s newest study answers a longstanding question in the field of innate immunity.

Scientists have long wondered how one protein, NLRP3, can promote inflammation in response to a wide range of seemingly unrelated stimuli.

Dr. Chen, Professor of Molecular Biology and Director of UT Southwestern’s Center for Inflammation Research, this month received the 2019 Breakthrough Prize in Life Sciences for identifying the DNA sensing enzyme cGAS (cyclic GMP-AMP synthase), which sounds the alarm to set off an innate immune response inside cells.

In the current study, published today in Nature, Dr. Chen investigated another immune system pathway that involves the NLRP3 protein, which is instrumental in the cell’s assembly of the multiprotein complex called the inflammasome. In response to a plethora of noxious agents that range from toxins to cholesterol crystals, the inflammasome triggers the pathway for inflammatory cell death, or pyroptosis from the Greek word pyro, meaning fire. The inflammasome also increases the body’s production of immune system substances, such as interleukins, that aid in the body’s immune response.

In addition, the NLRP3 protein underlies inflammation in a group of autoinflammatory diseases called cryopyrin-associated periodic syndromes (CAPS), which includes familial cold autoinflammatory syndrome (FCAS), gout, and a form of brain-cell inflammation associated with Alzheimer’s disease.

“A longstanding question in this field is how NLRP3 can be activated by many diverse agents that don’t appear to share any chemical or structural similarities,” said Dr. Chen, a Howard Hughes Medical Institute Investigator who holds the George L. MacGregor Distinguished Chair in Biomedical Science as well as a professorship in the Center for the Genetics of Host Defense at UT Southwestern. “These findings provide a new avenue for developing therapeutics that target the NLRP3 pathway for the treatment of inflammatory diseases.”

Through a combination of biochemical, imaging, and genetic approaches, Dr. Chen and postdoctoral researcher Dr. Jueqi Chen, the study’s lead author and no relation, discovered a previously unknown structural change within the cells.

They found that diverse stimuli all cause the cellular organelle called the trans-Golgi network (TGN) to break apart into giant vesicles, or fluid-filled sacs. These vesicles contain a special lipid component (PI4P) that binds to a specific region of NLRP3. This binding triggers a series of events leading to activation of the inflammasome.

“The NLRP3 inflammasome is unique in that it can be triggered by a large array of stimuli,” Dr. Chen said. “This study finds that rather than directly recognizing the noxious agents, the NLRP3 inflammasome detects a structural change caused by a range of different agents that cause cellular damage. In fact, NLRP3 activation is reminiscent of the ‘guard model’ that plants use to combat diverse threats by monitoring host targets that have been altered, the so-called pathogen-induced-altered-self approach.

“By binding to the disassembled trans-Golgi network vesicles as the ‘altered self,’ NLRP3 indirectly senses a large variety of pathogen- and danger-associated molecules,” he added.

Source:

https://www.utsouthwestern.edu/newsroom/articles/year-2018/innate-immunity.html

Tagged with:

About author

Related Articles