Not sure if “symptoms” is quite the right word here, but it’s what MIT News is using. Apparently, it’s been noticed for around a decade and half that when autistic kids get fevers, they seem less autistic. Now, a study from MIT and Harvard Medical School might have found how this works:
In a study of mice, the researchers found that in some cases of infection, an immune molecule called IL-17a is released and suppresses a small region of the brain’s cortex that has previously been linked to social behavioral deficits in mice.
“People have seen this phenomenon before […] but it’s the kind of story that is hard to believe, which I think stems from the fact that we did not know the mechanism,” says Gloria Choi, the Samuel A. Goldblith Career Development Assistant Professor of Applied Biology and an assistant professor of brain and cognitive sciences at MIT.
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Choi and Jun Huh, an assistant professor of immunology at Harvard Medical School, are the senior authors of the study, which appears in Nature today. The lead authors of the paper are MIT graduate student Michael Douglas Reed and MIT postdoc Yeong Shin Yim.
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Choi and Huh have previously explored other links between inflammation and autism. In 2016, they showed that mice born to mothers who experience a severe infection during pregnancy are much more likely to show behavioral symptoms such as deficits in sociability, repetitive behaviors, and abnormal communication. They found that this is caused by exposure to maternal IL-17a, which produces defects in a specific brain region of the developing embryos. This brain region, S1DZ, is part of the somatosensory cortex and is believed to be responsible for sensing where the body is in space.
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The researchers began by studying mice that exhibited behavioral symptoms due to exposure to inflammation during gestation. They injected these mice with a bacterial component called LPS, which induces a fever response, and found that the animals’ social interactions were temporarily restored to normal.
Further experiments revealed that during inflammation, these mice produce IL-17a, which binds to receptors in S1DZ — the same brain region originally affected by maternal inflammation. IL-17a reduces neural activity in S1DZ, which makes the mice temporarily more interested in interacting with other mice.
If the researchers inhibited IL-17a or knocked out the receptors for IL-17a, this symptom reversal did not occur. They also showed that simply raising the mice’s body temperature did not have any effect on behavior, offering further evidence that IL-17a is necessary for the reversal of symptoms.
“This suggests that the immune system uses molecules like IL-17a to directly talk to the brain, and it actually can work almost like a neuromodulator to bring about these behavioral changes,” Choi says. “Our study provides another example as to how the brain can be modulated by the immune system.”
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The researchers then performed the same experiments in three additional mouse models of neurological disorders. These mice lack a gene linked to autism and similar disorders — either Shank3, Cntnap2, or Fmr1. These mice all show deficits in social behavior similar to those of mice exposed to inflammation in the womb, even though the origin of their symptoms is different.
Injecting those mice with LPS did produce inflammation, but it did not have any effect on their behavior. The reason for that, the researchers found, is that in these mice, inflammation did not stimulate IL-17a production. However, if the researchers injected IL-17a into these mice, their behavioral symptoms did improve.
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“It was amazing to discover that the same immune molecule, IL-17a, could have dramatically opposite effects depending on context: Promoting autism-like behaviors when it acts on the developing fetal brain and ameliorating autism-like behaviors when it modulates neural activity in the adult mouse brain. This is the degree of complexity we are trying to make sense of,” Huh says.