Immunity is continuously evolving by evolutionary mechanisms shaped by pathogenic stimuli of different kinds. Man-made nanomaterials (NMs) have been developed in the last decades and represent a novel challenge for our immune system, especially when applied to medical science. Toxicological studies of such nanoparticles (NPs) revealed that size, shape, and surface chemistry are key parameters to understand their noxious effects on cellular mechanisms. Less is known on the immune reactions to NMs since prolonged exposure data are not so detailed as the results for acute administration. The importance of immunity to biocompatible NPs is underlined by their increasing use as drug or gene delivery carriers in common pharmaceutical preparations and vaccines. In the latter case, the immunomodulatory properties of NMs allow their use also as efficient adjuvants to enhance the innate immune response. In the current manuscript, the authors discuss the main concepts in this fast-growing field by restricting our view to NMs with consolidated application in biomedicine.

Interleukin (IL)-22 is produced from immune cells such as T helper (Th)22 cells, Th17/22 cells, and group 3 innate lymphoid cells. IL-22 signals via the IL-22 receptor 1 (IL-22R1) and the IL-10 receptor 2 (IL-10R2). As the IL-22R1/IL-10R2 heterodimer is preferentially expressed on border tissue between the host and the environment, IL-22 is believed to be involved in border defense. Epidermal keratinocytes are the first-line skin barrier and express IL-22R1/IL-10R2. IL-22 increases keratinocyte proliferation but inhibits differentiation. Aryl hydrocarbon receptor (AHR) is a chemical sensor and an essential transcription factor for IL-22 production. In addition, AHR also upregulates the production of barrier-related proteins such as filaggrin in keratinocytes, suggesting a pivotal role for the AHR-IL-22 axis in regulating the physiological skin barrier. Although IL-22 signatures are elevated in atopic dermatitis and psoriasis, their pathogenic and/or protective implications are not fully understood.

Atopic dermatitis (AD) is characterized by skin barrier disruption, type 2 immune dysregulation, chronic pruritus, and abnormal colonization by Staphylococcus aureus (S. aureus). Tapinarof, an aryl hydrocarbon receptor modulator, has been demonstrated to attenuate the development of AD in clinical studies. Recently, we found that tapinarof upregulated the expression of filaggrin and loricrin, which are essential proteins in skin barrier functions. Paradoxically, tapinarof induced interleukin (IL)-24 secretion by normal human keratinocytes. IL-24 is produced by T helper 2 lymphocytes and keratinocytes following stimulation by type 2 cytokines, and IL-24 is upregulated in the skin of patients with AD. Furthermore, IL-24 contributes to skin barrier disruption and hyperplasia in AD, and it may exacerbate skin inflammatory responses, itch, and S. aureus infection. In this review, we summarized the current findings regarding the detrimental role of IL-24 in AD, thereby suggesting that co-treatment of tapinarof with therapeutics that block IL-24 signaling may represent a promising strategy for managing AD.