The researchers, who reported their finding Dec. 1 in Nature, were studying a set of immune cells called group 3 innate lymphoid cells (ILC3s), which help the immune system tolerate beneficial microbes and suppress inflammation in the intestines and other organs throughout the body. They discovered a unique subset of these ILC3s that circulate in the bloodstream and can infiltrate the brain — and, to their surprise, do not quench inflammation but instead ignite it.

The scientists called this subset inflammatory ILC3s, and found them in the central nervous system of mice with a condition modeling MS. Instead of constraining the immune response, this subset of ILC3s spurred another group of immune cells called T cells to attack myelinated nerve fibers, leading to MS-like disease symptoms. The researchers detected similar inflammatory ILC3s in the peripheral blood and cerebrospinal fluid of MS patients.

“This work has the potential to inform our understanding of, and potential treatments for, a broad variety of conditions involving T-cell infiltration of the brain,” said senior author Dr. Gregory Sonnenberg, associate professor of microbiology and immunology in medicine in the Division of Gastroenterology and Hepatology and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.

MS affects more than two million people worldwide. Other conditions that feature chronic brain inflammation afflict tens of millions more and include Alzheimer’s and Parkinson’s diseases. There is also evidence that neuroinflammation develops naturally with aging and is a major factor in age-related cognitive decline, and more recently inflammatory T-cell responses in the brain have been linked to neurological symptoms associated with SARS-CoV-2 infection.

The researchers have shown in recent work that ILC3s residing in the gut act as sentinels and immune regulators, suppressing inflammation — including inflammatory T-cell activity — and warding off cancer. In the new study, they examined the roles of ILC3s in the brain, and found, contrary to their expectation, that ILC3s are not normally present in the brain under healthy conditions but can infiltrate the brain from the bloodstream during inflammation. When they do infiltrate the central nervous system, they have pro-inflammatory rather than anti-inflammatory effects.

The researchers showed with a mouse model of MS that these inflammatory ILC3s in the brain function as antigen-presenting cells: They display bits of myelin protein, the main ingredient in the insulating layer around nerve fibers, to T cells — prompting them to attack myelin, causing the nerve damage that gives rise to disease signs. They found the inflammatory ILC3s in close association with T cells in regions of active inflammation and nerve damage in the mouse brains.

“The infiltration of these inflammatory ILC3s to the brains and spinal cords of mice coincides with the onset and peak of disease,” said first author John Benji Grigg, a Weill Cornell Graduate School of Medical Sciences doctoral candidate in the Sonnenberg laboratory. “Further, our experimental data in mice demonstrate these immune cells play a key role in driving the pathogenesis of neuro-inflammation.”

The researchers discovered that they could prevent MS-like disease in the animals by removing from the ILC3s a key molecule called MHCII, which normally is used in the antigen-presenting process — the removal essentially blocks the cells’ ability to activate myelin-attacking T cells.

“Despite our very best disease-modifying therapies for MS, patients continue to progress, and since disease onset is early in life, they face the prospect of permanent physical and cognitive disability,” said co-author Dr. Tim Vartanian, professor of neuroscience in the Feil Family Brain and Mind Institute at Weill Cornell Medicine, chief of the division of multiple sclerosis and neuro-immunology and a professor of neurology in the Department of Neurology at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center. “Identification of inflammatory ILC3s with antigen presentation capabilities in the central nervous system of people with MS offers a new strategic target to prevent nervous system injury.”

Finally, the researchers discovered that ILC3s that reside in other tissues in the body can be programmed, in effect, to counter the activity of brain-infiltrating T cells, preventing the MS-like condition disease in mice.

This work was completed in close collaboration with Dr. Ari Waisman, director of the Institute for Molecular Medicine at the University Medical Center of Johannes Gutenberg University Mainz, where the researchers built on prior research demonstrating that there are gut-resident ILC3s that display antigens to T cells in a slightly different way to promote T-cell inactivity, or “tolerance.” The researchers demonstrated that by experimentally exposing these tolerance-inducing intestinal ILC3s to myelin, they could block neuroinflammatory T-cell activity and the development of MS-like disease in the mice.

The work therefore points to the possibility that MS and potentially many other inflammatory conditions could someday be treated either by directly inhibiting the activity of inflammatory ILC3s that infiltrate the brain, or by targeting self-antigens to the intestinal ILC3s that promote tolerance in other tissues, Dr. Sonnenberg said.

But a new study in the Journal of the International AIDS Society has local and global implications for successfully treating both mental health and HIV/AIDS in settings like South Africa — or even Miami, the epicenter of new cases in the United States.

In the study, an international team of researchers — led by the University of Miami’s Steven Safren and two colleagues — demonstrated the effectiveness of training nurses in public HIV clinics to deliver a specially adapted cognitive behavior therapy (CBT) to help people with depression and uncontrolled HIV adhere to their prescribed medication regiment. CBT is a proven approach for changing faulty or unhelpful thinking or behavioral patterns.

“We know that treating HIV-positive people who are clinically depressed with antidepressants alone does not affect their viral loads. Their depression may improve, but their adherence does not,” said Safren, professor of psychology and director of the University’s Center for HIV/AIDS Research and Mental Health. “So, given the global shortage of mental health professionals, we showed it is possible to train nurses to deliver cognitive-behavioral therapy for adherence and depression (CBT-AD), an intervention that successfully addresses both clinical depression and uncontrolled HIV.”

Safren, who joined the University in 2015 from Harvard Medical School, conducted the study in a poor township just outside of Cape Town, South Africa, with fellow researchers John A. Joska, director of the HIV Mental Health Research Unit and professor of psychiatry at the University of Cape Town, and Conall O’Cleirigh, associate professor of psychology at Harvard and director of Behavioral Medicine at Massachusetts General Hospital.

For their study, the researchers recruited 161 patients with uncontrolled HIV/AIDS and clinical depression from four public health clinics in the township of Khayelitsha. Although a medical officer could prescribe antidepressants to the patients, the clinics have limited psychological services — as does the country in general. According to the study, South Africa only has 0.28 psychiatrists and 0.32 psychologists per 100,000 people.

At the onset of the study, all participants received the usual enhanced care for clinically depressed HIV-AIDS patients who did not achieve viral suppression after receiving the first month of their antiretroviral medication. That customary treatment included another prescription and follow-up meetings with an adherence counselor.

But half the patients were also randomly assigned to attend eight CBT-AD sessions, where specially trained nurses integrated strategies for treating depression with adherence counseling that included modules on life skills, depression, relaxation, mood monitoring, and problem-solving.

The idea, Safren said, was to help patients “turn down the volume” of their mental health symptoms, so they would be more open to counseling on the benefit of taking their medication. To track their adherence, the patients also received an electronic pill box that, every time it was opened, transmitted a real-time signal to a web server.

And, researchers found, the task-shared approach delivered by nurses proved effective. Patients who completed the CBT-AD sessions were more than 2.5 times more likely to achieve undetectable viral loads that those who underwent the usual care.

Now, Safren noted, the next step will be for the research team to evaluate how to sustainably implement the CBT-AD approach in South Africa, or even South Florida. He said the task-shared approach could be viable in Miami, where there are fewer services to help people achieve viral suppression than in other U.S. cities with large populations of people living with the virus.

“South Africa has the most cases of HIV/AIDS in the world and Miami is the city with the highest incidence of new cases in the U.S. — so there is a parallel,” Safren pointed out. “And unlike places like New York or Massachusetts, where people are more likely to be virally suppressed, Florida doesn’t have the same public health resources. If, for example, you’re an HIV patient at Massachusetts General or Fenway Health, where I used to work, and you miss your visit, or your viral load becomes uncontrolled, social workers will swoop in and provide assistance. That doesn’t happen as often in Florida and other places in the U.S. with less public health HIV/AIDS funding.”

In addition to Safren, Joska, and O’Cleirigh, other co-authors on the study included Jasper S. Lee, a Ph.D. student, and Sierra A. Bainter, an assistant professor, both in the Department of Psychology at the University; as well as researchers from the University of Maryland, College Park; the University of Science and Technology in Mbarara, Uganda; the University of Washington in Seattle; and Stellenbosch University in Stellenbosch, South Africa.

The gold standard for imaging and diagnosing diseases within the retina, OCT has yet to find widespread use as an imaging technique for other parts of the body due to its inability to return clear images from more than a millimeter beneath the skin’s surface.

Duke researchers found that tilting the light source and detector used in the technique increases OCT’s imaging depth by almost 50%, putting skin diagnoses within reach. The “dual-axis” approach opens new possibilities for OCT to be used in applications such as spotting skin cancer, assessing burn damage and healing progress, and guiding surgical procedures.

The results appear online on December 1 in the open access journal Biomedical Optics Express.

“It’s actually a fairly simple technique that sounds like something out of Ghostbusters — you get more power when you cross the beams,” said Adam Wax, professor of biomedical engineering at Duke. “Being able to use OCT even 2 or 3 millimeters into the skin is extremely useful because there are a lot of biological processes happening at that depth that can be indicative of diseases like skin cancer.”

Standard OCT is analogous to ultrasound but uses light instead of sound. A beam of light is shined down into an object, and by measuring how long it takes for it to bounce back, computers can deduce what the internal structure of the object looks like. It has become the go-to technology for imaging and diagnosing retinal diseases because the retina is so thin and easily accessible through the eye’s transparent cornea and lens.

Most other biological tissues, however, scatter and reflect light, making it difficult to penetrate with standard OCT approaches. The deeper the light goes, the more likely it is to get lost in the sample and miss the device’s detection.

In the new technique, researchers instead point the light at the object at a slight angle and set up the detector at an equal and opposite angle, creating a dual-axis. This allows the detector to benefit from the slight scattering angle introduced by the object’s physical nature.

“By tilting the light source and detector, you increase your chances of collecting more of the light that’s scattering off at odd angles from a tissue’s depths,” said Evan Jelly, a doctoral student in Wax’s laboratory and first author of the paper. “And OCT is so sensitive that just a little bit more of that scattered light is all you need.”

According to Jelly, researchers have tried this dual-axis approach in other imaging modalities. But through his experiments, Jelly discovered how to apply this to OCT. His key discovery was that the depth of the focal point of light within the tissue makes a large difference in how well the dual-axis approach works.

However, there is a catch: The greater the angle used to identify deeper signal, the smaller the field of view becomes. To get around this issue, Jelly devised a method of scanning the focus of the narrower window through various depths of the tissue and then using a computational algorithm to combine the data into a single image.

In the paper, Wax and Jelly tested this approach with fabricated tissues and hairless mice to benchmark its performance against standard OCT to see what information it could reveal in a live animal’s skin. The controlled experiments showed that the dual-axis OCT approach does tend to outperform the standard setup. And in the live mice, the dual-axis OCT was able to image the tip of a needle 2 millimeters beneath the skin’s surface, where 1.2 millimeters is traditionally the landmark depth.

“The dual-axis OCT gave us images and information from the layers of skin where blood and molecular exchanges are occurring, which is extremely valuable for detecting signs of diseases,” said Jelly. “The technology is still in its infancy, but it is primed to be highly successful for biosensing or guiding surgical procedures.”

This research was funded by the National Science Foundation (CBET-2009841, IIP-1827560).

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Materials provided by Duke University. Original written by Ken Kingery. Note: Content may be edited for style and length.