In brief

A study using a mouse model of eczema reveals time-related differences in the severity of allergic reactions and offers potential solutions for better managing inflammatory skin conditions in patients.

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Allergies flare like clockwork

11 Sep 2023

Researchers discover that circadian rhythms control immune responses and may affect how our skin's immune system responds to allergies.

We hurry to work during the morning commute and wind down with relaxing family time in the evenings. Similarly, biological processes that include immune responses wax and wane to rhythms orchestrated by the body’s internal clock.

Kenji Kabashima, Senior Principal Investigator at A*STAR, in collaboration with the Skin Research Institute of Singapore (SRIS) and Kyoto University Graduate School of Medicine, Japan, explained that immune cells in the skin are also influenced by circadian patterns, which has implications on the severity of allergic reactions throughout the day.

“A better understanding may improve time-dependent preventive medicine, examinations, and treatment [of allergic skin reactions],” explained Kabashima.

Using an experimental mouse model of eczema (an inflammatory skin condition), Kabashima’s team investigated how the timing of allergen exposure affects the activity of immune cells in the skin.

The animals were exposed to a chemical allergen known to elicit an inflammatory response in the skin to mirror an allergic reaction called contact hypersensitivity. Interestingly, the group that was sensitised at night experienced more skin swelling (an indicator of an exaggerated immune response) than the group that received the treatment during the day.

Kabashima’s team also observed increased cell growth and the production of immune signalling molecules in the lymph nodes of mice sensitised at night. They hypothesised that these differences were a result of the natural hormonal oscillations that stimulated immune cells via the β2-adrenergic receptor (β2AR).

In follow-up experiments, the researchers observed increased ear swelling and an influx of immune cells into the lymph nodes when they chemically activated β2ARs in day-sensitised mice. Conversely, chemically blocking β2AR in night-sensitised mice depleted immune cells in the lymph nodes and alleviated ear swelling.

Kabashima said that these findings may offer insights into how to better manage patients living with inflammatory skin conditions. Mice are nocturnal creatures and their immune systems likely guard them against allergens they may encounter during night-time activities. Humans on the other hand, are likely to be more sensitive to skin allergens during the day, explained Kabashima, who suggests that applying topical treatments during the day might help control flare-ups.

“The daytime topical application of proactive therapy may also enhance its preventive effect,” added Kabashima, who together with the team, has plans to conduct clinical studies in patients with eczema to optimise the timing of topical treatments.

Since the study in the Singapore Immunology Network (SIgN), Kabashima has joined the A*STAR Skin Research Labs (A*SRL) as a Senior Principal Investigator to continue his work on atopic dermatitis, its pathogenesis and potential treatments.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).

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Miyake, T., Egawa, G., Chow, Z., Asahina, R., Otsuka, M., et al. Circadian rhythm affects the magnitude of contact hypersensitivity response in mice. Allergy  77 (9), (2022). | article

About the Researcher

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Kenji Kabashima

Senior Principal Investigator

A*STAR Skin Research Labs (A*SRL)
Kenji Kabashima graduated from Kyoto University in 1996 and underwent Medicine and Dermatology training at the United States Naval Hospital in Yokosuka Japan, Kyoto University Hospital and University of Washington Medical Center. His research interests include atopic dermatitis, its pathogenesis and potential treatments. He is also working on gene-targeted fluorescent chemical probes to visualise cells to help understand the mechanisms underpinning skin homeostasis. Previously with the Singapore Immunology Network (SIgN), Kabashima currently serves as a Senior Principal Investigator at the A*STAR Skin Research Labs (A*SRL).

This article was made for A*STAR Research by Wildtype Media Group