Keratinocytes as Immune Regulators: Linking Skin Stress to Antibody Production
Nowadays, skin is not only considered as a physical barrier but also as an important immune organ that can influence systemic immune responses. Previous studies mainly focused on immune cells such as dendritic cells or T cells when explaining systemic humoral immunity. However, the role of keratinocytes in regulating systemic antibody responses was not well understood. Because keratinocytes are the most abundant cells in the epidermis and are the first cells to encounter environmental stress or infection, it was necessary to investigate whether they can influence systemic humoral immunity.
The purpose of this research was to understand how keratinocytes contribute to systemic humoral immune responses. The researchers found that when keratinocytes experience stress such as infection or ultraviolet exposure, their metabolic pathway called the mevalonate pathway becomes activated. Through this process, a metabolite called farnesyl pyrophosphate (FPP) accumulates in keratinocytes. FPP activates the ion channel TRPV3, which increases calcium signaling inside the cells. As a result, keratinocytes produce cytokines such as IL-6 and chemokines such as CCL20 that can stimulate immune responses.
These signals from keratinocytes influence immune cells including dendritic cells and T follicular helper (Tfh) cells. The activation of these cells promotes germinal center formation in lymphoid organs, where B cells differentiate into plasma cells and produce antibodies. In this way, signals that start from keratinocytes in the skin can lead to stronger systemic humoral immunity. This study shows that keratinocytes can actively regulate immune responses, suggesting that skin-derived metabolic signals may play an important role in controlling systemic antibody production.
출처: https://pubmed.ncbi.nlm.nih.gov/41781621/
