Immune-System Gene Expression Changes With the Seasons

Dopico XC, Evangelou M, Ferreira RC et al.Widespread seasonal gene expression reveals annual differences in human immunity and physiology. Nature Communications 2015;6:7000. doi: 10.1038/ncomms8000

This study adds a whole new wrinkle to the endless debate about whether inflammatory jointsand weather. The researchers find, apparently for the first time, that "different transcriptional landscapes are present in the peripheral immune system during different seasons."

Their research could help to explain the observed seasonality of infectious and inflammatory diseases, including rheumatoid arthritis and cardiovascular disease.

They analyzed mRNA expression levels in peripheral blood mononuclear cells (PBMCs), blood counts, and circulating levels of inflammatory proteins from human populations that differ ethnically and geographically, with the following results:

•  PBMCs from children in a German cohort show more than a 1.5-fold difference between winter and summer in expression of genes controlling the circadian anti-inflammatory protein ARNTL (aryl hydrocarbon receptor nuclear translocator-like protein), regardless of time of day when the samples were taken. This confirms the stated hypothesis in their study.

•  Prostaglandin receptors are more highly expressed in the winter in the German samples.

•  The glucocorticoid receptor NR3C1 was strongly correlated with ARNTL, with lowest expression in the winter.

•  The study showed distinct patterns of genes with expression highest in the summer or winter.

•  Replicating the results in two independent cell collections (from type 1 diabetes patients in the UK and patients with asthma from Australia, United
Kingdom/Ireland, United States and Iceland), they found 147 genes with common seasonality among all populations except those in the long, dark winter of Iceland. Australian samples showed opposite expression patterns from those collected in the northern hemisphere, when defined by calendar months.

•  Expression of these "seasonal genes" correlated strongly with the expression of 13 genes associated with immune cell types.  Total numbers of white blood cells, lymphocytes, monocytes, basophils, eosinophils, neutrophils, and platelets showed seasonality in the peripheral circulation in banked samples from healthy adult donors.

•  Pro-inflammatory processes were more frequent among the genes with increased expression in winter months, including B-cell receptor signalling and chemokine signalling. Expression of acute-phase complement activator, C-reactive protein, and other factors associated with response to vaccines also vary seasonally.

•  In the cells from German children, the concentration of the sIL-6R protein associated with impaired IL-6 signalling, and with protection from rheumatoid arthritis as well as cardiovascular disease and type 1 diabetes, was increased in winter months.

•  Immune-system genes in cells from The Gambia, "completely different" from those in the UK cohort, showed highest expression during the rainy season, when the burden of diseases such as malaria is highest. 

Two so-called "housekeeping genes" often used as standards in lgene expression studies, B2M and GAPDH, did not show seasonal variation.

The authors observe that their findings may have implications for the interpretation of results of many other studies.