Dr-Oliver-Harrison-in-his-labMost people have about 21 square feet of skin — and inside your skin is an entire world called the microbiome. This world includes many different types of bacteria, viruses and fungi. As you grow up, your immune system learns which microbes help keep you healthy, and which are infection-causing enemies. But sometimes that process goes wrong.

The immune system might mistakenly attack good bacteria in the skin, fail to fight off harmful bacteria, or keep attacking even when bad bacteria is gone. But few immunologists have studied how the immune system interacts with the skin microbiome, and why those processes go wrong.

Oliver Harrison, DPhil, joined BRI in 2019 to explore this new frontier. He’s part of a new generation of BRI scientists, taking our research in new directions. He has already made some key findings — including uncovering a mysterious type of T cell with a critical job — and he recently landed a $2.9 million NIH grant to propel this promising work.

“We still don't know a lot of basics about how the body responds to these microbes,” Dr. Harrison says. “First, we want to learn more about how those responses work. Then we can ask ‘does your immune system carry out processes that we didn’t know about?’ And, if so, can we learn how to speed them up to heal wounds or slow them down to curb autoimmunity?”

A T cell with a side job

Dr. Harrison’s team started this work aiming to better understand how the immune system interacts with bacteria in your skin. They wanted to learn more about how immune cells called commensal T cells know which bacteria to attack and which bacteria to leave alone.

Their findings opened up a new realm of understanding – and led to many new questions. In the past, scientists typically thought interactions between the immune system and any bacteria (good or bad) caused inflammation. The research team found that was true for bad bacteria – but not for good bacteria. When immune cells saw good bacteria, they acknowledged them, but did not cause inflammation.  

T-cell-pull-quote“This is very striking and a lot different from the immune responses that we understand and have studied to date,” Dr. Harrison says. “This observation suggests that there are entirely distinct immune mechanisms and pathways for dealing with these good bacteria that we don’t yet understand. Learning more about this response to healthy bacteria can give scientists insight into how the immune system should respond and what goes wrong in disease.”

The research team also found that some commensal T cells had another job: In addition to recognizing bacteria, they help with healing.

“They have this moonlighting role where they turn on genes and proteins that help heal,” Dr. Harrison says. “That’s rare in immune cells and especially rare in T cells. This opens up a whole new avenue to explore how T cells sense their environment and adapt rapidly to deal with problems.”

Harnessing natural responses for good

Dr. Harrison will use his new grant to learn more about commensal-specific T cells in the skin, how they interact with bacteria and how they help your body heal. This could pave the way to answering key questions: How exactly do these cells fight off bad bacteria or promote healing? How can we fix these processes if they go wrong?

“We basically want to understand these natural mechanisms that regulate the immune system and learn how to harness them for good,” Dr. Harrison says.

Down the road, this research could inform how to speed up or slow down the immune system in infection and disease. Doctors might want to speed up the immune system to heal things like diabetic foot ulcers or in settings like the military to treat serious wounds. Slowing down the immune response could be beneficial for conditions like atopic dermatitis, where the immune response is too strong, causing skin irritation. 

“There’s always a balance,” Dr. Harrison says. “We want to slow the immune system down enough to stop atopic dermatitis, but not so much that it impairs the ability to heal wounds. Knowing more about how these responses are separately controlled might help us find the right balance.”

Further explorations

Dr. Harrison managed to make all of this progress despite the challenges of getting his new lab up and running in the time of COVID-19. Moving forward, he is excited to collaborate with other BRI scientists and grow his team. He plans to continue his explorations of the microbiome in the skin and also in the gut. He says there’s one silver lining of starting a lab during a pandemic.

“I’m really glad I’m doing it at BRI,” he says. “Throughout the pandemic, our scientists have stayed so committed to their work, often making big upheavals in their lives to make it come to fruition. The best thing about BRI is the people — the pandemic didn’t change that. I look forward to everyone being back in-person.”

Fighting Diseases

April 16, 2021

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