Targeting Immune Cells In The Gut: A New Treatment For Depression?


Johns Hopkins Medicine researchers have discovered an immune cell in the intestine that affects the gut microbiome, which can impact brain functions associated with depression. Published in Nature Immunology,  the study found that targeting these immune cells with medication or therapy may be possible to develop new treatments for depression.

“The results of our study highlight the previously unrecognized role of intestinal gamma delta T cells (γδ T cells) in modifying psychological stress responses, and the importance of a protein receptor known as dectin-1, found on the surface of immune cells, as a potential therapeutic target for the treatment of stress-induced behaviors,” said Atsushi Kamiya, MD, PhD, professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and the study’s senior author.

According to researchers, Dectin-1, a receptor, binds to specific proteins or antigens to activate immune cells in a particular manner. The receptor might be involved in immune-inflammatory responses and microbiome changes in the colon of mice, implying its role in stress responses through γδ T cells in the intestinal immune system.

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Kamiya and the team investigated the relationship between gut microbiota imbalance and stress-induced behaviors related to depression. Using chronic social defeat stress (CSDS) tests, they examined the impact of stress on the gut microbiota in mice. The researchers simulated various stress-inducing environments and classified the mice as stress-resilient or stress-susceptible based on their social interactions.

Next, they gathered fecal samples from the mice and put them through genetic analysis to detect the variety of bacteria in their gut microbiota. The findings indicated that stress-susceptible mice had lower microbial diversity in their intestines than stress-resilient mice. The stressed mice were also lacking in the beneficial bacteria Lactobacillus johnsonii.

“We found that stress increased the γδ T cells, which in turn increased social avoidance,” said the study’s lead author Xiaolei Zhu, MD,  PhD. “However, when the stressed mice were given L. johnsonii, social avoidance decreased, and the γδ T cells went to normal levels, suggesting that CSDS-induced social avoidance behavior may be the result of lower levels of the bacteria and γδ T cell changes.”

To gain insight into human brain responses, the researchers examined the gut microbiota of people with major depressive disorder (MDD) and non-depressed people. The study enrolled 66 participants aged 20 years or older, from June 2017 to September 2020, recruited from three hospitals in Tokyo, Japan. Of the participants, 32 had MDD (17 women and 15 men), and 34 (18 women and 16 men) without MDD were included in the control group.

“Despite the differences in intestinal microbiota between mice and humans, the results of our study indicate that the amount of Lactobacillus in the gut may potentially influence stress responses and the onset of depression and anxiety,” says Kamiya.

Further research is required to fully comprehend the effect of γδ T cells in the gut's immune system on brain function and the role of dectin-1 in other cell types along the gut-brain axis during stress.

Said Kamiya: “These early-stage findings show that in addition to probiotic supplements, targeting drugs to such types of receptors in the gut immune system may potentially yield novel approaches to prevent and treat stress-induced psychiatric symptoms such as depression.”

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