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Animal Research Yields New Discoveries in Immunity and Autoimmune Diseases

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Immunity is a complex area of research with wide-ranging applications in human health. From the discovery of the potentially immune-boosting properties of a common vitamin to the identification of a new connection between gender and immunity, the field of animal research has generated scientific discoveries providing valuable insights into immunity.

Food and Immunity

From “an apple a day keeps the doctor away” to the latest discoveries in animal research, the connection between immunity and what we consume has deep roots.

A new study from Francis Crick Institute, the National Cancer Institute, and Aalborg University in Denmark identified not apples, but vitamin D as a potential immune-boosting ingredient. The study found that vitamin D promotes the growth of a certain type of bacteria that enhances resistance to cancer in mice.

Vitamin D is known to play a key role in immune modulation, boosting the function of immune cells. The new study expanded on those findings by exploring the effects of vitamin D in mice. Mice were given either a standard diet or one rich in vitamin D.

After being transplanted with cancer, the mice that received the vitamin D–enriched diet exhibited a higher immune response compared to the control mice. The vitamin D mice also demonstrated a more favorable reaction to immunotherapy treatment.

To extrapolate this data to humans, the team analyzed data from 1.5 million people in Denmark and found that low levels of vitamin D correlated with a higher incidence of cancer. As with the mouse study, individuals with higher levels of vitamin D responded more favorably to immune-based cancer treatments.

A different study, from Johns Hopkins, identified a link between complement proteins in breast milk and immunity. Breast milk already has many proven and suspected benefits, including some related to immunity.

In the new study, the researchers shed light on how breast milk improves immunity by focusing on complement proteins in breast milk. They found that mouse breast milk boosts the health of pups by eliminating some types of gut bacteria, thereby protecting them from certain bacterial infections.

The team engineered mice to lack critical complement genes. Pups who nursed from the engineered mice were substantially more susceptible to Citrobacter rodentium infections. Pups who nursed from normal lactating mice showed only minor signs of infection. 

The component in the mouse breast milk that performed this function is also present in human breast milk, which opens the door to potential new explorations of how complement proteins boost immunity in human babies.

Immunity and Gender

There are many biological differences between men and women, and a new study out of Stanford University has identified another key difference: their susceptibility to autoimmune diseases.

Nearly 50 million people in the United States have some form of autoimmune disease, such as multiple sclerosis, lupus, rheumatoid arthritis, and type 1 diabetes, and 80% of them are women. In a study with mice, the scientists found that autoimmune conditions could be linked to a molecule that contributes to shutting down one of the two X chromosomes carried by women.

In a process called X-chromosome inactivation, one of these two X chromosomes is silenced by an RNA molecule called Xist. The proteins that Xist uses to inactivate the X chromosome are related to autoimmune disorders.

To investigate this process, the research team genetically modified male mice to produce Xist. The modified mice showed significantly higher levels of immune disease. It’s still unclear what role Xist plays in the onset of autoimmune disease, but the discovery may help researchers develop new targeted therapies.

Controlling Immunity Via the Brain

New research with mice out of Yale University has discovered that one important immune system controller actually lies outside the immune system itself—in the brain.

The team found that a group of cells in the brainstem acts as a central control center for the body’s immune system, dialing immunity responses up or down as needed.

To test whether the brain responds to signals from the immune system, the researchers injected mice with lipopolysaccharide, an immune stimulant, then scanned the brains of the mice to see if any areas were being activated. They found evidence in an area of the brain stem called the caudal nucleus of the solitary tract, which is the first stop for incoming information from the body to the brain via the vagus nerve.

The team used genetic engineering to insert new receptors into the neurons, allowing them to switch the neurons on and off. To test the reactions of the mice, they gave them the immune stimulant and switched the neurons off. The mice immediately experienced a massive immune response akin to severe sepsis or a cytokine storm in humans. When they administered the immune stimulant with the neurons turned on, the mice demonstrated a strong anti-inflammatory response.

The findings could have significant implications for clinical applications, with the potential for new medications to regulate immune disorders via the brain.

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