The epidermis is the primary interface between the body and the environment. Life first emerged in aquatic environments, and even in terrestrial organisms, internal tissues originated in an aquatic setting. Therefore, establishing a waterproof barrier is essential to preserve bodily functions. Most amphibians inhabit areas near water. The integumentary system of reptiles consists of scales, birds are covered by feathers, and most mammals have hair. However, humans have minimal hair on their skin. As a result, human skin undergoes significant changes in response to environmental humidity.

According to the literature, evidence suggests that cutaneous pathologies, including the severity of atopic dermatitis, are influenced by seasonal variations [1-3]. A decrease in environmental humidity is particularly relevant for managing skin conditions. Conversely, a recent report described the mechanisms underlying the urban dry island effect [4]. In modern urban environments, residents are exposed to ambient humidity levels below the natural range.

In this concise review, I synthesize the literature on the effects of environmental humidity on skin physiology and explore potential mechanisms underlying these effects. Previous studies have shown that temperature also affects the homeostatic function of epidermal keratinocytes [5-8]. In this paper, I focus on the effects of changes in environmental humidity on the epidermis, rather than temperature. The definition of a dry environment varies among the papers discussed. Generally, an absolute humidity of 50% or less is considered dry, but some reports define a humid environment as around 100% and examine the effects of lower humidity in comparison. This article provides definitions as used in each paper.

Several studies have examined the impact of seasonal variations on the prevalence of dermatological conditions. Research indicates that the prevalence of skin diseases is influenced by seasonal factors. A previous review noted that people living in countries near the equator, such as in northern Europe and North America, are exposed to harsh winter weather and may experience dry, itchy skin. The authors suggested that low environmental humidity during winter may be a crucial factor [1].

A study at the Children’s Hospital of Nanjing Medical University found a correlation between low humidity (relative humidity [RH] < 50%) and high humidity (RH > 80%) and skin allergies. The authors concluded that changes in humidity might be a risk factor for allergic reactions [2].

A study in Helsinki found a seasonal pattern in the prevalence of atopic dermatitis, with increased cases in January, February, March, and November, and decreased cases in July and August. A significant correlation was identified between temperature and UV index; however, no association was found between precipitation and air humidity [3]. The literature suggests a correlation between changes in environmental humidity and the development of skin pathology, as well as various other factors [1, 2].

As previously mentioned, seasonal changes and alterations in humidity can induce itchiness, as seen in atopic dermatitis [1]. A previous report indicated that pruritus associated with atopic dermatitis is attributable to an increase in nerve fibers in the epidermis [25]. However, our previous findings showed that the density of nerve fibers in the epidermis of patients with atopic dermatitis was lower than that observed in healthy controls [26]. A study also demonstrated lower nerve fiber density in patients with both atopic dermatitis and psoriasis [27]. Therefore, the underlying cause of pruritus in atopic dermatitis and psoriasis may be multifactorial. As reported previously, the release of thymic stromal lymphopoietin (TSLP) from keratinocytes has been shown to induce itch [28].

As previously mentioned, stress from environmental humidity changes induces a series of pathological responses in epidermal keratinocytes. Declines in the water-impermeable barrier function have been observed in atopic dermatitis [29]. Furthermore, a recent review suggested that cytokines released from epidermal keratinocytes and dysfunction of barrier homeostasis induce a series of allergic reactions [30]. To develop an effective new strategy for treating itch in atopic dermatitis and psoriasis, it is necessary to focus on the physiology of keratinocytes.

A series of studies have suggested that epidermal keratinocytes might possess a sensory system for humidity; however, the mechanism remains to be elucidated. TRPV4, a known sensor of changes in osmotic pressure [31], could serve as the key humidity sensor in the epidermis. Furthermore, TRPV4 activation and expression have been observed to increase in corneal epithelia following exposure to hypotonic solutions, which simulate dry conditions [32]. As previously demonstrated, topical application of a TRPV4 agonist accelerates barrier recovery following disruption [5]. Consequently, TRPV4 emerges as a promising candidate for the role of a humidity sensor.

We have also demonstrated that exposure of cultured human keratinocytes to air leads to an increase in intracellular calcium concentration and ATP secretion [33]. Evidence has also shown that application of ATP induces IL-6 expression and secretion from cultured human keratinocytes [34]. Another study demonstrated that, following ATP stimulation, IL-1β is released from keratinocytes and may induce inflammation [35]. Current research suggests that ATP plays a crucial role in inflammatory mechanisms induced by environmental factors.

According to the literature, epidermal keratinocytes have been shown to produce and release various endocrine factors [36, 37]. Since the last century, A. Slominski and his colleagues have published a series of papers indicating the presence of endocrinological systems in the epidermis [38-41]. In the context of wound healing, an increase in cortisol synthesis within the epidermis has been observed [42]. These findings prompted further investigation into the impact of a dry environment on cortisol synthesis in epidermal keratinocytes [43]. A skin equivalent model was incubated for 48 hours under two distinct environmental conditions: dry (relative humidity less than 10%) and humid (relative humidity approximately 100%). Subsequently, cortisol secretion and the mRNA levels of the cortisol-synthesizing enzyme steroid 11β-hydroxylase (CYP11B1), as well as IL-1β, were evaluated. Cortisol secretion increased threefold, while CYP11B1 and IL-1β mRNA increased 38-fold and sixfold, respectively, under dry conditions compared to humid conditions. Occlusion with a water-impermeable plastic membrane partially blocked the increases in cortisol secretion and CYP11B1 and IL-1β mRNA expression in the dry condition [43].

In addition, as previously mentioned, environmental dryness has been shown to stimulate the release of various inflammatory cytokines from epidermal keratinocytes [21, 23]. Furthermore, oxytocin, a neurohormone that regulates human emotions, is produced by keratinocytes [44]. We previously proposed the hypothesis that these factors may influence the brain and emotional state [45]. Therefore, environmental dryness may not only induce dermatological conditions but also systemic problems, including psychological abnormalities.

As described above, a decrease in environmental humidity can induce barrier dysfunction and inflammatory responses. Moreover, it might influence whole-body pathology, including psychological problems. Previous reports have indicated that the phenomenon of the “dry island effect” has been documented within metropolitan areas [4]. In addition, a recent proposal [46] has suggested that human skin would undergo significant alterations in water content under spaceflight conditions. Homo sapiens are creatures that have demonstrated the ability to persist in the face of environmental changes. This adaptation has enabled humanity to inhabit the entire planet and, in the future, possibly also outer space. However, given the evolutionary history of Homo sapiens, which occurred in forest and savanna environments, the species must now adapt to different artificial environments. To prepare for future life, it is imperative to consider epidermal physiology in the context of drastically changing environmental conditions.