Breaking News
January 20, 2019 - Liver Transplant Survival May Improve With Race Matching
January 20, 2019 - Study implicates hyperactive immune system in aging brain disorders
January 20, 2019 - Cancer Diagnosis May Quadruple Suicide Risk
January 20, 2019 - Parkinson’s disease experts devise a roadmap
January 20, 2019 - Research brings new hope to treating degenerative brain diseases
January 20, 2019 - Scientists pinpoint a set of molecules that wire the body weight center of the brain
January 20, 2019 - Researchers get close to developing elusive blood test for Alzheimer’s disease
January 20, 2019 - UCLA researchers demonstrate new technique to develop cancer-fighting T cells
January 20, 2019 - Researchers discover how cancer cells avoid genetic meltdown
January 20, 2019 - Exercise makes even the ‘still overweight’ healthier: study
January 20, 2019 - University of Utah to establish first-of-its-kind dark sky studies minor in the US
January 20, 2019 - School-based nutritional programs reduce student obesity
January 20, 2019 - Improved maternity care practices in the southern U.S. reduce racial inequities in breastfeeding
January 20, 2019 - New enzyme biomarker test indicates diseases and bacterial contamination
January 20, 2019 - Republican and Democratic governors have different visions to transform health care, say researchers
January 20, 2019 - Researchers discover that spin flips happen in only half a picosecond in the course of a chemical reaction
January 20, 2019 - Suicide Risk Up More Than Fourfold for Cancer Patients
January 20, 2019 - Doctors find 122 nails in Ethiopian’s stomach
January 20, 2019 - UV disinfection technology eliminates up to 97.7% of pathogens in operating rooms
January 20, 2019 - Researchers discover mechanism which drives leukemia cell growth
January 20, 2019 - AHA: Infection as a Baby Led to Heart Valve Surgery for Teen
January 20, 2019 - Injection improves vision in a form of childhood blindness
January 20, 2019 - Multiple sclerosis therapies delay progression of disability
January 20, 2019 - New study finds infrequent helmet use among bike share riders
January 20, 2019 - Clearing up information about corneal dystrophies
January 20, 2019 - Researchers describe new behavior in energy metabolism that refutes existing evidence
January 20, 2019 - New study takes first step toward treating endometriosis
January 20, 2019 - Researchers find how GREB1 gene promotes resistance to prostate cancer treatments
January 20, 2019 - Replacing Sitting Time With Activity Lowers Mortality Risk
January 20, 2019 - A simple, inexpensive intervention makes birth safer for moms and babies in parts of Africa
January 19, 2019 - New anti-inflammatory compound acts as ‘surge protector’ to reduce cancer growth
January 19, 2019 - Significant flaws found in recently released forensic software
January 19, 2019 - New Leash on Life? Staying Slim Keeps Pooches Happy, Healthy
January 19, 2019 - Men and women remember pain differently
January 19, 2019 - Rising air pollution linked with increased ER visits for breathing problems
January 19, 2019 - Study uses local data to model food consumption patterns among Seattle residents
January 19, 2019 - The brain’s cerebellum plays role in controlling reward and social behaviors, study shows
January 19, 2019 - Relationship between nurse work environment and patient safety
January 19, 2019 - Pioneering surgery restores movement to children paralyzed by acute flaccid myelitis
January 19, 2019 - Genetic variants linked with risk tolerance and risky behaviors
January 19, 2019 - New research provides better understanding of our early human ancestors
January 19, 2019 - First-ever tailored reporting guidance to improve patient care and outcomes
January 19, 2019 - 4.6 percent of Massachusetts residents have opioid use disorder
January 19, 2019 - New study suggests vital exhaustion as risk factor for dementia
January 19, 2019 - New antibiotic discovery heralds breakthrough in the fight against drug-resistant bacteria
January 19, 2019 - Ural Federal University scientists synthesize a group of multi-purpose fluorophores
January 19, 2019 - Researchers identify new therapeutic target in the fight against chronic liver diseases
January 19, 2019 - Preparation, characterization of Soyasapogenol B loaded onto functionalized MWCNTs
January 19, 2019 - FDA Approves Ontruzant (trastuzumab-dttb), a Biosimilar to Herceptin
January 19, 2019 - Tobacco use linked with higher use of opioids and sedatives
January 19, 2019 - Study delves deeper into developmental dyslexia
January 19, 2019 - Anti-vaccination movement one of the top health threats in 2019 says WHO
January 19, 2019 - Newly developed risk score more effective at identifying type 1 diabetes
January 19, 2019 - Highly effective protocol to prepare cannabis samples for THC/CBD analysis
January 19, 2019 - Prinston Pharmaceutical Inc. Issues Voluntary Nationwide Recall of Irbesartan and Irbesartan HCTZ Tablets Due to Detection of a Trace Amount of Unexpected Impurity, N-Nitrosodiethylamine (NDEA) in the Products
January 19, 2019 - How does solid stress from brain tumors cause neuronal loss, neurologic dysfunction?
January 19, 2019 - $14.7 million partnership to supercharge vaccine development
January 19, 2019 - Ian Fotheringham receives Charles Tennant Memorial Lecture award
January 19, 2019 - Brain vital signs detect neurophysiological impairments in players with concussions
January 19, 2019 - Lack of job and poor housing conditions increased likelihood of people attending A&E
January 19, 2019 - Novel targeted drug delivery system improves conventional cancer treatments
January 19, 2019 - Rutgers study finds gene responsible for spread of prostate cancer
January 19, 2019 - Complications Higher Than Expected for Invasive Lung Tests
January 19, 2019 - 3-D printed implant promotes nerve cell growth to treat spinal cord injury
January 19, 2019 - Automated texts lead to improved outcomes after total knee or hip replacement surgery
January 19, 2019 - Poor cardiorespiratory fitness could increase risk of future heart attack, finds new study
January 19, 2019 - Drinking soft drinks while exercising in hot weather may increase risk of kidney disease
January 19, 2019 - Formlabs 3D prints anatomical models
January 19, 2019 - Heart-Healthy Living Also Wards Off Type 2 Diabetes
January 19, 2019 - Teaching Kids to Be Smart About Social Media (for Parents)
January 19, 2019 - Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease
January 19, 2019 - Researchers examine how spray from showers and toilets expose us to disease causing bacteria
January 19, 2019 - Behavioral experiments confirm that additional neurons improve brain function
January 19, 2019 - New study compares performance of real-time infectious disease forecasting models
January 19, 2019 - Obesity can be risk factor for developing renal cell carcinoma, confirms study
January 19, 2019 - New regulation designs on cigarette packs direct smokers’ attention to health warnings
January 19, 2019 - QIAGEN receives first companion diagnostic approval in Japan
January 19, 2019 - Study explores role of Dunning-Kruger effect in anti-vaccine attitudes
January 19, 2019 - Hepatitis C-infected patients with a history of liver cancer can be treated with antivirals
January 19, 2019 - Study shows how gut bacteria affect the treatment of Parkinson’s disease
Western diet depletes artery-protecting immune cells

Western diet depletes artery-protecting immune cells

image_pdfDownload PDFimage_print
Cross section of an aorta from a mouse that was fed a high-fat, high-cholesterol diet, which accelerates the build-up of plaque. The large red plaque on the inside of the aorta was labeled with oil based stain, which highlights lipids. Credit: Dr. Dalia Gaddis, La Jolla Institute for Allergy and Immunology

New research from scientists at the La Jolla Institute For Allergy and Immunology shows how a diet high in fat and cholesterol depletes the ranks of artery-protecting immune cells, turning them into promoters of inflammation, which exacerbate atherosclerotic plaque buildup that occurs in cardiovascular disease. The team has also found that high density lipoproteins (HDL)—more commonly known as “good cholesterol”—counteract this process, helping the protective immune cells maintain their identity and keep arteries clear.

The study published March 15, 2018, in the journal Nature Communications was led by LJI scientists Dalia Gaddis, Ph.D., and Catherine Hedrick, Ph.D.

Inflammation is a key contributor to the hardening and narrowing of the arteries known as atherosclerosis—a condition that can lead to heart attack or stroke. Hedrick’s lab is investigating the roles that immune cells play in this process and how the function of different immune cells can change as atherosclerosis progresses.

“People think atherosclerosis is just about cholesterol, diet, and exercise, but it’s actually an immune disease,” says Dalia Gaddis, Ph.D., a postdoctoral researcher in Hedrick’s lab. “The blockage of arteries is very much due to the immune system reacting to excess cholesterol and lipids in the walls of blood vessels.”

Different subsets of immune cells have opposing roles in atherosclerosis—some contribute to the build-up of plaques, and others protect against it, Gaddis explains. In the current study, she and her colleagues focused on protective cells called regulatory T cells, or Tregs. Tregs prevent the development of atherosclerosis. But researchers have found that when mice are fed a high-fat, high-cholesterol diet—also known as a Western diet—their numbers of protective Tregs decline.

Gaddis wanted to track regulatory T cells in the mice during this process to find out what was happening to them. Typically, scientists look for a protein called Foxp3 to identify regulatory T cells, but this marker is lost when the cells are reprogrammed into another cell type. So Gaddis used mice in which regulatory T cells would be tagged with two fluorescent markers. One, a yellow marker on the Foxp3 protein, allowed her to easily recognize all regulatory T cells. The second tag—a red one—would also be produced by regulatory T cells and then retained regardless of their fate, enabling the researcher team to track the cells in the blood vessels and atherosclerotic plaques even if they changed their identity and stopped making Foxp3.

To begin her experiments, Gaddis fed some of the mice a western diet. After 15 weeks of this regime, she examined the animals’ immune cells. The differences were clear. Gaddis found regulatory T cells in the aorta—the large artery that carries blood from the heart to the rest of the body—in all of the mice. But in the animals that had consumed the Western diet, she also saw significant numbers of “ex Tregs” in the lymph nodes and aorta.

Molecular analyses revealed that some of the former regulatory T cells had become follicular helper T cells (Tfh). These are critical components of the immune system that help the body fight off viral and bacterial infections. Little was known, however, about how they impact atherosclerosis.

With further experiments, Gaddis and her colleagues established that Tfh cells promote atherosclerosis. By blocking the generation of Tfh cells, the scientists could reduce the development of plaques in the arteries of mice fed the Western diet.

The team next wanted to know whether HDL, which removes excess cholesterol from cells, might protect against atherosclerosis by preventing the loss of regulatory T cells. They tested this idea by administering the primary component of HDL, a protein called apolipoprotein AI, to their mice. With this treatment, regulatory T cells resisted the effects of the Western diet and did not change into Tfh cells.

Although it’s not yet known whether regulatory T cells undergo the same conversion in humans, the finding gives a clearer picture of how diet and the immune system interact to shape cardiovascular risk.

“With a western diet, protective cells change to damaging cells, causing more inflammation,” says Gaddis. “What we’re finding is that HDL—the good cholesterol—actually helps shield the protective cells against the damaging changes that occur during atherosclerosis plaque development.”


Explore further:
Promoting regulatory T cell production may help control atherosclerosis

More information:
Dalia E. Gaddis et al, Apolipoprotein AI prevents regulatory to follicular helper T cell switching during atherosclerosis, Nature Communications (2018). DOI: 10.1038/s41467-018-03493-5

Journal reference:
Nature Communications

Provided by:
La Jolla Institute for Allergy and Immunology

Tagged with:

About author

Related Articles