Does it ever seem like you get sick more often in the winter? Some postulate that this is simply because we spend more time crowded inside with other people when it’s cold out. This could be one reason that winter is often referred to as “cold and flu” season. However, it’s not necessarily that simple. Doctors and scientists have tracked other seasonal trends in illness that have nothing to do with our proximity to others. Many illnesses, especially autoimmune diseases such as rheumatoid arthritis, become worse in winter months, only to inexplicably improve in warm weather.

In the past decade, numerous studies examining seasonality and the immune system have confirmed that immunity, inflammation and other components of health do, in fact, have a seasonal rhythm – and that this rhythm is caused by differences in gene expression throughout the seasons. In fact, about a quarter of the body’s genes appear to be more active during certain parts of the year. In short, in addition to having circadian, infradian and ultradian rhythms, our bodies have a seasonal rhythm as well.

Seasonality and the Immune System

It has long been recognized that nongenetic factors can influence certain seasonal rhythms of the body. Take, for example, the above-mentioned fact that being around other people indoors more often can boost the risk of infectious disease. Or the idea that the cold weather increase in mental illness and conditions like Seasonal Affective Disorder (SAD) is at least partially due to lower levels of vitamin D from less sunlight.

While these types of factors definitely contribute to seasonal rhythms in many aspects of our health, they are not the only cause. A chronobiological study on seasonality and the immune system performed at the University of Cambridge and published in Nature Communications, found that seasonal changes in gene expression affect everything from inflammation, gestational diabetes and heart disease to blood and adipose composition and immune system response from season to season.

Testing Gene Expression

Gene expression is the process by which genetic instructions are used to create the proteins needed to perform and participate in particular body functions. In a nutshell, our genes hold the blueprints for proteins. When a particular gene is expressed, the protein whose code the gene carries will be made within the cell expressing it. The differences between various types of cells in the body are simply due to the different proteins expressed.

To test gene expression, the University of Cambridge team took blood and tissue samples from 16,000 people in far-flung areas of both the Northern and Southern Hemisphere. Several factors were measured, including the types and amounts of cells in the blood as well as the protein composition of cells in both blood and tissues. The result? Several genes showed seasonal variation consistently across different populations, in nations as diverse as Gambia and the UK.

ARNTL, Immunity and Winter

In the Cambridge study, one gene that showed different expression in summer and winter was ARNTL. This gene has already been the subject of several studies, including research in circadian biology. ARNTL has been linked to the circadian rhythm as well as to a range of medical disorders including gestational diabetes, inflammation and heart disease. In the recent study, ARNTL was found to be far more active in the summer and less so in the winter.

ARNTL has been shown to protect against inflammation in rats and is believed to have the same effect in humans. Thus, differences in gene expression from season to season may explain why diseases involving inflammation, such as rheumatoid arthritis and heart disease, usually become worse in winter.

Another set of genes, which has been connected to the body’s response to vaccination, appeared to be more active in the winter, suggesting that timing vaccines more specifically could enhance the body’s subsequent immune response. This connection between the seasonal expression of the ARNTL gene and others and certain diseases presents new treatment possibilities for people with chronic disease.

Another more recent study on seasonality and the immune system examined blood samples collected from over 329,000 participants over the course of 10 years. Researchers found obvious differences in inflammation markers and white blood cell counts in different seasons, and even at different times of the day. Based on this information, it appeared that people may be more susceptible to certain diseases during less active times of the day (such as nighttime) and in the winter. The daily and seasonal changes in inflammation markers and white blood cell counts did not appear to be related to vitamin D levels, or environmental factors.

Why Is Seasonal Variation Important?

Why does the season affect gene expression and the immune system in particular? Scientists believe that this is not a coincidence but rather a survival mechanism. Many of the seasonal variations in gene expression that were discovered were quite useful. For example, people who lived in Gambia had higher levels of immune cells in their blood during the period when malaria is most common — from June to September. At the same time, the increase in inflammation and the lower threshold needed to trigger immune response seen in the winter months is similarly adaptive. In this case, the body is creating more inflammatory proteins to better fight off the many illness-causing microorganisms that are more likely to be encountered during the winter.

However, this seasonal rhythm can become maladaptive in modern times, when chronic conditions made worse by inflammation cause more ill effects than the contagious illnesses we associate with cold weather months. One good example is Type I or juvenile diabetes. Many more cases of this autoimmune form of diabetes are diagnosed in the winter months, likely due to the increase in inflammation and immune cells in the body during this time.

In addition to confirming that there is a marked seasonal rhythm in health, this study in chronobiology has led to many new questions as well. How can this knowledge of seasonal rhythm be used to treat illnesses with seasonal variation? What mechanism leads to the variation in immunity and inflammation over the seasons? Future studies will be sure to answer these and other questions about circadian biology and our bodies’ internal clocks.