“Never get old” is something I hear frequently from my older patients as it brings all the unwanted medical issues. The skin, like every other organ, is not resistant to the effects of ageing. For example, skin infections in the elderly tend to be more common and frequently, more persistent. How often have you noticed verrucae are more stubborn to treatment in older patients or that fungal infection is so much more common?
A forthcoming paper in the Journal of Investigative Dermatology may offer some insight into this under-researched phenomenon. Researchers from Harvard Medical School (1) compared skin samples from the young and old. They demonstrated that older skin had much lower numbers of Langerhans cells present in the epidermis. The Langerhans cell [LC] (which I have covered in an earlier blog) is a cell that feely roams the epidermis and plays a key role in the sensing of infection in the skin and is able to initiate the appropriate immune response. It therefore logically follows that any decline in their numbers reduces the skins ability to detect and eradicate potential microbial invasion.
So why the decline? The researchers looked at three possible explanations – either they had “moved out” (migrated away), had died (known as apoptosis) or weren’t being replenished. The researchers did establish that apoptosis or migration of the Langerhans cells was not an issue suggesting renewal maybe the problem. Langerhans cells are derived from specific monocytes (that carrier a marker known as the CD14+) that reside in the dermis. This work showed that the numbers of these progenitor cells were also reduced in the dermis.
Why this is the case was further examined by the research team who showed that a chemical mediator produced by the basal layer keratinocytes (CXCL14) is a potent mediator which when released can recruit Langerhans cells by transforming the CD14+ dermal monocytes. When levels of this mediator were measured in young and old skin it was found to be depleted in older skin, suggesting reduction in this chemical was responsible for the drop in Langerhans cells. This finding was confirmed when CXCL14 was injected into older skin samples a significant increase in Langerhans cells was observed.
So, what does this mean?
There is no doubt that Langerhans cells play a key role in maintaining immune surveillance in the skin. Acting like a policeman on the beat they are able to watch out for any invading pathogens and if detected, they will present them to T cells which are able to generate a specific immune response to rid the infection. Some infections are able to disable the Langerhans cell. For example, the wart (HPV) virus has been shown to be able to “blind” Langerhans cells to its present and thereby promote its persistence (2).
What this work has shown is that as we age, we see a natural decline in the numbers of Langerhans cells in our skin and consequently this may lead to more frequent and persistent skin infections in this age group. However, there is some light on the horizon as this work has shown that numbers of Langerhans cells can be increased by chemical modulation which may form the basis of a future treatments.
References
1. Hasegawa T, Feng Z, Yan Z, Ngo KH, Hosoi J, Demehri S. Reduction in human epidermal Langerhans cells with age is associated with decline in CXCL14-mediated recruitment of CD14+ monocytes. J Invest Dermatol. 2020:early view.
2. Fausch SC, Fahey LM, Da Silva DM, Kast WM. Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation. J Immunol. 2005;174(11):7172-8.