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Molecules that fight infection also act on the brain, inducing anxiety or sociability
Immune molecules called cytokines play important roles in the body’s defense against infection, helping to control inflammation and coordinating the responses of other immune cells. A growing body of evidence suggests that some of these molecules also influence the brain, leading to behavioral changes during illness.
Two new studies from MIT and Harvard Medical School, focused on a cytokine called IL-17, now add to that evidence. The researchers found that IL-17 acts on two distinct brain regions — the amygdala and the somatosensory cortex — to exert two divergent effects. In the amygdala, IL-17 can elicit feelings of anxiety, while in the cortex it promotes sociable behavior.
These findings suggest that the immune and nervous systems are tightly interconnected, says Gloria Choi, an associate professor of brain and cognitive sciences, a member of MIT’s Picower Institute for Learning and Memory, and one of the senior authors of the studies.
“If you’re sick, there’s so many more things that are happening to your internal states, your mood, and your behavioral states, and that’s not simply you being fatigued physically. It has something to do with the brain,” she says.
Jun Huh, an associate professor of immunology at Harvard Medical School, is also a senior author of both studies, which appear today in Cell. One of the papers was led by Picower Institute Research Scientist Byeongjun Lee and former Picower Institute research scientist Jeong-Tae Kwon, and the other was led by Harvard Medical School postdoc Yunjin Lee and Picower Institute postdoc Tomoe Ishikawa.
Behavioral effects
Choi and Huh became interested in IL-17 several years ago, when they found it was involved in a phenomenon known as the fever effect. Large-scale studies of autistic children have found that for many of them, their behavioral symptoms temporarily diminish when they have a fever.
In a 2019 study in mice, Choi and Huh showed that in some cases of infection, IL-17 is released and suppresses a small region of the brain’s cortex known as S1DZ. Overactivation of neurons in this region can lead to autism-like behavioral symptoms in mice, including repetitive behaviors and reduced sociability.
“This molecule became a link that connects immune system activation, manifested as a fever, to changes in brain function and changes in the animals’ behavior,” Choi says.
IL-17 comes in six different forms, and there are five different receptors that can bind to it. In their two new papers, the researchers set out to map which of these receptors are expressed in different parts of the brain. This mapping revealed that a pair of receptors known as IL-17RA and IL-17RB is found in the cortex, including in the S1DZ region that the researchers had previously identified. The receptors are located in a population of neurons that receive proprioceptive input and are involved in controlling behavior.
When a type of IL-17 known as IL-17E binds to these receptors, the neurons become less excitable, which leads to the behavioral effects seen in the 2019 study.
“IL-17E, which we’ve shown to be necessary for behavioral mitigation, actually does act almost exactly like a neuromodulator in that it will immediately reduce these neurons’ excitability,” Choi says. “So, there is an immune molecule that’s acting as a neuromodulator in the brain, and its main function is to regulate excitability of neurons.”
Choi hypothesizes that IL-17 may have originally evolved as a neuromodulator, and later on was appropriated by the immune system to play a role in promoting inflammation. That idea is consistent with previous work showing that in the worm C. elegans, IL-17 has no role in the immune system but instead acts on neurons. Among its effects in worms, IL-17 promotes aggregation, a form of social behavior. Additionally, in mammals, IL-17E is actually made by neurons in the cortex, including S1DZ.
“There’s a possibility that a couple of forms of IL-17 perhaps evolved first and foremost to act as a neuromodulator in the brain, and maybe later were hijacked by the immune system also to act as immune modulators,” Choi says.
Provoking anxiety
In the other Cell paper, the researchers explored another brain location where they found IL-17 receptors — the amygdala. This almond-shaped structure plays an important role in processing emotions, including fear and anxiety.
That study revealed that in a region known as the basolateral amygdala (BLA), the IL-17RA and IL-17RE receptors, which work as a pair, are expressed in a discrete population of neurons. When these receptors bind to IL-17A and IL-17C, the neurons become more excitable, leading to an increase in anxiety.
The researchers also found that, counterintuitively, if animals are treated with antibodies that block IL-17 receptors, it actually increases the amount of IL-17C circulating in the body. This finding may help to explain unexpected outcomes observed in a clinical trial of a drug targeting the IL-17-RA receptor for psoriasis treatment, particularly regarding its potential adverse effects on mental health.
“We hypothesize that there’s a possibility that the IL-17 ligand that is upregulated in this patient cohort might act on the brain to induce suicide ideation, while in animals there is an anxiogenic phenotype,” Choi says.
During infections, this anxiety may be a beneficial response, keeping the sick individual away from others to whom the infection could spread, Choi hypothesizes.
“Other than its main function of fighting pathogens, one of the ways that the immune system works is to control the host behavior, to protect the host itself and also protect the community the host belongs to,” she says. “One of the ways the immune system is doing that is to use cytokines, secreted factors, to go to the brain as communication tools.”
The researchers found that the same BLA neurons that have receptors for IL-17 also have receptors for IL-10, a cytokine that suppresses inflammation. This molecule counteracts the excitability generated by IL-17, giving the body a way to shut off anxiety once it’s no longer useful.
Distinctive behaviors
Together, the two studies suggest that the immune system, and even a single family of cytokines, can exert a variety of effects in the brain.
“We have now different combinations of IL-17 receptors being expressed in different populations of neurons, in two different brain regions, that regulate very distinct behaviors. One is actually somewhat positive and enhances social behaviors, and another is somewhat negative and induces anxiogenic phenotypes,” Choi says.
Her lab is now working on additional mapping of IL-17 receptor locations, as well as the IL-17 molecules that bind to them, focusing on the S1DZ region. Eventually, a better understanding of these neuro-immune interactions may help researchers develop new treatments for neurological conditions such as autism or depression.
“The fact that these molecules are made by the immune system gives us a novel approach to influence brain function as means of therapeutics,” Choi says. “Instead of thinking about directly going for the brain, can we think about doing something to the immune system?”
The research was funded, in part, by Jeongho Kim and the Brain Impact Foundation Neuro-Immune Fund, the Simons Foundation Autism Research Initiative, the Simons Center for the Social Brain, the Marcus Foundation, the N of One: Autism Research Foundation, the Burroughs Wellcome Fund, the Picower Institute Innovation Fund, the MIT John W. Jarve Seed Fund for Science Innovation, Young Soo Perry and Karen Ha, and the National Institutes of Health.
DIRNSA Fired
In “Secrets and Lies” (2000), I wrote:
It is poor civic hygiene to install technologies that could someday facilitate a police state.
It’s something a bunch of us were saying at the time, in reference to the vast NSA’s surveillance capabilities.
I have been thinking of that quote a lot as I read news stories of President Trump firing the Director of the National Security Agency. General Timothy Haugh.
A couple of weeks ago, I wrote:
We don’t know what pressure the Trump administration is using to make intelligence services fall into line, but it isn’t crazy to ...
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Silence among farmers
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Silence among farmersHumans fuel stronger cyclones
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Climate change and climate action are socially and politically divisive topics in many countries. In addition to contributing to political disparity, climate research is also affected by political context, with consequences not only for scientists but for society as well.Friday Squid Blogging: Two-Man Giant Squid
The Brooklyn indie art-punk group, Two-Man Giant Squid, just released a new album.
As usual, you can also use this squid post to talk about the security stories in the news that I haven’t covered.
Breakerspace image contest showcases creativity, perseverance
The MIT Department of Materials Science and Engineering Breakerspace transformed into an art gallery on March 10, with six easels arranged in an arc to showcase arresting images — black-and-white scanning electron microscope (SEM) images of crumpled biological structures alongside the brilliant hues of digital optical microscopy.
The images were the winning entries from the inaugural Breakerspace Microscope Image Contest, which opened in fall 2024. The contest invited all MIT undergraduates to train on the Breakerspace’s microscopic instruments, explore material samples, and capture images that were artistic, instructive, or technically challenging.
“The goal of the contest is to inspire curiosity and creativity, encouraging students to explore the imaging tools in the Breakerspace,” says Professor Jeffrey Grossman of the Department of Materials Science and Engineering (DMSE). “We want students to see the beauty and complexity of materials at the microscopic level, to think critically about the images they capture, and to communicate what they mean to others.”
Grossman was a driving force behind the Breakerspace, a laboratory and lounge designed to encourage MIT undergraduates to explore the world of materials.
The contest drew about 50 entries across four categories:
- Most Instructive, for images illustrating key concepts with documentation
- Most Challenging, requiring significant sample preparation
- Best Optical Microscope Image of a sample, rendered in color
- Best Electron Microscope Image, magnified hundreds or even thousands of times
Winners in the four categories received $500, and two runners-up received $100.
“By making this a competition with prizes, we hope to motivate more students to explore microscopy and develop a stronger connection to the materials science community at MIT,” Grossman says.
A window onto research
Amelia How, a DMSE sophomore and winner of the Most Instructive category, used an SEM to show how hydrogen atoms seep into titanium — a phenomenon called hydrogen embrittlement, which can weaken metals and lead to material failure in applications such as aerospace, energy, or construction. The image stemmed from How’s research in Associate Professor Cem Tasan’s research lab, through MIT’s Undergraduate Research Opportunities Program (UROP). She trained on the SEM for the contest after seeing an email announcement.
“It helped me realize how to explain what I was actually doing,” How says, “because the work that I’m doing is something that’s going into a paper, but most people won’t end up reading that.”
Mishael Quraishi, a DMSE senior and winner of Best SEM Image, captured the flower Alstroemeria and its pollen-bearing structure, the anther. She entered the contest mainly to explore microscopy — but sharing that experience was just as rewarding.
“I really love how electron images look,” Quraishi says. “But as I was taking the images, I was also able to show people what pollen looked like at a really small scale — it’s kind of unrecognizable. That was the most fun part: sharing the image and then telling people about the technique.”
Quraishi, president of the Society of Undergraduate Materials Scientists, also organized the event, part of Materials Week, a student-run initiative that highlights the department’s people, research, and impact.
Persistence in practice
The winner of the Most Challenging category, DMSE sophomore Nelushi Vithanachchi gained not just microscopy experience, but also perseverance. The category called for significant effort put into the sample preparation — and Vithanachchi spent hours troubleshooting.
Her sample — a carving of MIT’s Great Dome in silicon carbide — was made using a focused ion beam, a tool that sculpts materials by bombarding them with ions, or charged atoms. The process requires precision, as even minor shifts can ruin a sample.
In her first attempt, while milling the dome’s façade, the sample shifted and broke. A second try with a different design also failed. She credits her UROP advisor, Aaditya Bhat from Associate Professor James LeBeau’s research group, for pushing her to keep going.
“It was four in the morning, and after failing for the third time, I said, ‘I’m not doing this,’” Vithanachchi recalls. “Then Aaditya said, ‘No, we’ve got to finish what we started.’” After a fourth attempt, using the lessons learned from the previous failures, they were finally able to create a structure that resembled the MIT dome.
Anna Beck, a DMSE sophomore and runner-up for Best Electron Microscope Image, had a much different experience. “It was very relaxed for me. I just sat down and took images,” she says. Her entry was an SEM image of high-density polyethylene (HDPE) fibers from an event wrist band. HDPE is a durable material used in packaging, plumbing, and consumer goods.
Through the process, Beck gained insight into composition and microscopy techniques — and she’s excited to apply what she’s learned in the next competition in fall 2025. “In hindsight, I look at mine now and I wish I turned the brightness up a little more.”
Although 35 percent of the entries came from DMSE students, a majority — 65 percent — came from other majors, or first-year students.
With the first contest showcasing both creativity and technical skill, organizers hope even more students will take on the challenge, bringing fresh perspectives and discoveries to the microscopic world. The contest will run again in fall 2025.
“The inaugural contest brought in an incredible range of submissions. It was exciting to see students engage with microscopy in new ways and share their discoveries,” Grossman says. “The Breakerspace was designed for all undergraduates, regardless of major or experience level — whether they’re conducting research, exploring new materials, or simply curious about what something is made of. We’re excited to expand participation and encourage even more entries in the next competition.”
Lincoln Laboratory honored for technology transfer of hurricane-tracking satellites
The Federal Laboratory Consortium (FLC) has awarded MIT Lincoln Laboratory a 2025 FLC Excellence in Technology Transfer Award. The award recognizes the laboratory's exceptional efforts in commercializing microwave sounders hosted on small satellites called CubeSats. The laboratory first developed the technology for NASA, demonstrating that such satellites could work in tandem to collect hurricane data more frequently than previously possible and significantly improve hurricane forecasts. The technology is now licensed to the company Tomorrow.io, which will launch a large constellation of the sounder-equipped satellites to enhance hurricane prediction and expand global weather coverage.
"This FLC award recognizes a technology with significant impact, one that could enhance hourly weather forecasting for aviation, logistics, agriculture, and emergency management, and highlights the laboratory's important role in bringing federally funded innovation to the commercial sector," says Asha Rajagopal, Lincoln Laboratory's chief technology transfer officer.
A nationwide network of more than 300 government laboratories, agencies, and research centers, the FLC helps facilitate the transfer of technologies out of federal labs and into the marketplace to benefit the U.S. economy, society, and national security.
Lincoln Laboratory originally proposed and demonstrated the technology for NASA's TROPICS (Time-Resolved Observations of Precipitation structure and storm Intensity with a Constellation of SmallSats) mission. For TROPICS, the laboratory put its microwave sounders on low-cost, commercially available CubeSats for the first time.
Of all the technology used for sensing hurricanes, microwave sounders provide the greatest improvement to forecasting models. From space, these instruments detect a range of microwave frequencies that penetrate clouds, allowing them to measure 3D temperature, humidity, and precipitation in a storm. State-of-the-art instruments are typically large (the size of a washing machine) and hosted aboard $2 billion polar-orbiting satellites, which collectively may revisit a storm every six hours. If sounders could be miniaturized, laboratory researchers imagined, then they could be put on small satellites and launched in large numbers, working together to revisit storms more often.
The TROPICS sounder is the size of a coffee cup. The laboratory team worked for several years to develop and demonstrate the technology that resulted in a miniaturized instrument, while maintaining performance on par with traditional sounders for the frequencies that provide the most useful tropical cyclone observations. By 2023, NASA launched a constellation of four TROPICS satellites, which have since collected rapidly refreshed data of many tropical storms.
Now, Tomorrow.io plans to increase that constellation to a global network of 18 satellites. The resulting high-rate observations — under an hour — are expected to improve weather forecasts, hurricane tracking, and early-warning systems.
"This partnership with Tomorrow.io expands the impact of the TROPICS mission. Tomorrow.io’s increased constellation size, software pipeline, and resilient business model enable it to support a number of commercial and government organizations. This transfer to industry has resulted in a self-sustaining national capability, one that is expected to help the economy and the government for years to come," says Tom Roy, who managed the transfer of the technology to Tomorrow.io.
The technology transfer spanned 18 months. Under a cooperative research and development agreement (CRADA), the laboratory team adapted the TROPICS payload to an updated satellite design and delivered to Tomorrow.io the first three units, two of which were launched in September 2024. The team also provided in-depth training to Tomorrow.io and seven industry partners who will build, test, launch, and operate the future full commercial constellation. The remaining satellites are expected to launch before the end of this year.
"With these microwave sounders, we can set a new standard in atmospheric data collection and prediction. This technology allows us to capture atmospheric data with exceptional accuracy, especially over oceans and remote areas where traditional observations are scarce," said Rei Goffer, co-founder of Tomorrow.io, in a press release announcing the September launches.
Tomorrow.io will use the sounder data as input into their weather forecasts, data products, and decision support tools available to their customers, who range from major airlines to governments. Tomorrow.io's nonprofit partner, TomorrowNow, also plans to use the data as input to its climate model for improving food security in Africa.
This technology is especially relevant as hurricanes and severe weather events continue to cause significant destruction. In 2024, the United States experienced a near-record 27 disaster events that each exceeded $1 billion in damage, resulting in a total cost of approximately $182.7 billion, and that caused the deaths of at least 568 people. Globally, these storm systems cause thousands of deaths and billions of dollars in damage each year.
“It has been great to see the Lincoln Laboratory, Tomorrow.io, and industry partner teams work together so effectively to rapidly incorporate the TROPICS technology and bring the new Tomorrow.io microwave sounder constellation online,” says Bill Blackwell, principal investigator of the NASA TROPICS mission and the CRADA with Tomorrow.io. “I expect that the improved revisit rate provided by the Tomorrow.io constellation will drive further improvements in hurricane forecasting performance over and above what has already been demonstrated by TROPICS.”
The team behind the transfer includes Tom Roy, Bill Blackwell, Steven Gillmer, Rebecca Keenan, Nick Zorn, and Mike DiLiberto of Lincoln Laboratory and Kai Lemay, Scott Williams, Emma Watson, and Jan Wicha of Tomorrow.io. Lincoln Laboratory will be honored among other winners of 2025 FLC Awards at the FLC National Meeting to be held virtually on May 13.
Troy Hunt Gets Phished
In case you need proof that anyone, even people who do cybersecurity for a living, Troy Hunt has a long, iterative story on his webpage about how he got phished. Worth reading.