• Immune response
• Regulating the microbiota
What is already known on this topic
Multiple sclerosis (MS) is an autoimmune disorder that removes the protective myelin sheath around nerve cells, leading to muscle weakness, blindness, and even death. The gut microbiota has been linked to MS, but the exact role of gut microbes remains unclear.What this research adds
Working in a mice model of MS, researchers have found that loss of the expression of a specific immune molecule called IL-17 reduced MS-like symptoms. IL-17-producing immune cells isolated from mice lacking IL-17 were fully capable of inducing disease when transferred into mice with normal IL-17 expression. But these cells did not cause MS symptoms when transferred into mice lacking IL-17, which suggests that IL-17 produced from immune cells is not required to establish the disease. Transferring gut bacteria from control mice into IL-17-deficient mice or triggering IL-17 expression in gut-lining cells restored the animals’ susceptibility to disease.Conclusion
The findings show that IL-17 molecules from the gut can influence autoimmune diseases in the central nervous system by regulating the gut microbiota rather than directly triggering brain inflammation. The results could also inform the development of treatment approaches targeting IL-17 signaling in long-term inflammatory diseases such as MS.
Multiple sclerosis (MS) is an autoimmune disorder that removes the protective myelin sheath around nerve cells, leading to muscle weakness, blindness, and even death. Now, a new study shows that inflammatory molecules in the brain may not be the primary culprit. Rather, two types of immune molecules from the gut appear to play a key role in the development of the disease.
The findings, published in Science Immunology, could inform the development of treatment approaches for long-term inflammatory diseases.
Several studies have linked the gut microbiota to MS, but the exact role of gut microbes remains unclear. What’s more, scientists have long known that two types of inflammatory molecules, known as IL-17A and IL-17F, are involved in the development of MS. However, it’s debated whether these molecules are actually driving the disease.
To address this question, Ari Waisman at Johannes Gutenberg-University in Mainz and his colleagues analyzed a mouse model of MS.
Immune response
Loss of either IL-17A or IL-17F expression reduced MS-like symptoms in mice, and the immune cells that produce IL-17 — known as TH17 cells — isolated from these mice were fully capable of inducing disease when transferred into mice with normal IL-17 expression.
However, these cells did not cause MS-like symptoms when transferred into mice lacking IL-17, suggesting that IL-17 produced from TH17 is not required to establish the disease. This also suggests that there is another mechanism that blocks MS development in mice lacking IL-17.
When IL-17-deficient mice and control mice were housed together — a process that allows the gut microbiota to be transferred between animals, the mutant mice showed more disease symptoms than their wild-type counterpart.
Regulating the microbiota
Because both IL-17A and IL-17F are linked to gut health, the researchers hypothesized that IL-17 loss may have disturbed the composition of the gut microbiota, making mice resistant to MS development. Indeed, fecal samples from IL-17-deficient mice showed microbiota changes compared to control animals.
Transferring gut bacteria from control mice into IL-17-deficient mice increased the rodents’ susceptibility to disease. Restoring IL-17 expression in gut-lining cells had similar effects, the researchers found.
The findings show that IL-17 molecules from the gut can influence autoimmune diseases in the central nervous system by regulating the gut microbiota rather than directly triggering brain inflammation, the researchers say. The results could also inform the development of treatment approaches targeting IL-17 signaling in MS and other chronic inflammatory diseases.
