The Skin A battleground

We are exposed to millions of germs every moment, yet we manage to stay healthy. We are also exposed to harmful ultraviolet rays (UV), but we are still alive. Despite our bodies comprising 70% water, we lead terrestrial lives. Isn't it surprising?

The body’s largest organ, the skin, works relentlessly to face the environment and make the above possible. The skin is specially equipped with a ‘skin barrier’ that acts as border control, constantly dealing with environmental threats. On the other hand, it communicates with internal organs such as the gut and the brain, ensuring our environmental adaptation. Due to the absence of blood vessels, a nutrient-deficient environment always prevails in the skin. Despite its critical role, the skin does not get much attention or care as an important organ. Overall, it is not an overstatement to compare the skin to the battalion in the country’s borders who work hard to maintain the internal system functional with lesser highlights.

The image depicts the human skin and its barrier formed by keratinocytes. The cartoon, in the form of a soldier, represents keratinocyte life-cycle stages with protective weapons (organelles). Each stage corresponds to the in vivo skin layers (light background). The sword represents active protection through cytokines and AMPs (antimicrobial peptides) secreted from the respective cells mentioned above. (Image courtsey: Sarmistha; Image background was from Biorender.com).

The skin barrier is the surface of our body that we see and touch, and it sheds on a monthly basis. It is a multilayered epithelium having specialized features to cope with the environment. A unique cell type called keratinocytes form the skin barrier. Keratinocytes delve into different physiological/functional forms in their life-cycle. All these functional forms are differently equipped with organelles, the subcellular compartments that collectively take care of body’s protection (depiction in the image). As shown, they receive melanosomes from melanocytes (another cell type of the skin) for protection from UV (ultraviolet rays). When we go out to the sun and get exposed to UV, keratinocytes signal melanocytes to donate melanosomes to them, which then helps in photoprotection, and as a result, we see skin tanning. In the next stage of their life-cycle, keratinocytes produce multifunctional lysosomes that help in cell survival and also protect from microbes. In the second last stage keratinocytes are equipped with lamellar bodies, a specialized organelle that otherwise is not present in any other cells. Lamellar bodies secrete components that form the hydrophobic barrier and the antimicrobial barrier and also regulate the renewal of the skin barrier over time. Cytokines produced from keratinocytes (the sword) additionally protect the skin and also regulate overall skin barrier health. This is how healthy skin is maintained and protects our body.

What happens when the skin barrier is damaged in accidents or in any kind of mechanical injury? This is the situation when extruders the pathogenic microbes enter the body! This is the time when additional support from the body’s interior (mainly the immune system) is required. Keratinocytes, as soldiers on the body’s surface, secrete chemicals (cytokines) that send emergency signals to the other cells to prevent infection and heal the wound. As a first response, platelet-mediated blood clotting gives temporary protection by blocking the wound. Next, immune cells come to the site of injury and destroy the microbes, which give long-term protection. In addition, keratinocyte also signals stem cells to proliferate (divide to increase in number) quickly, migrate to the wound site, and heal the tissue.

Therefore, a constant battle is on, and keratinocytes are the soldiers active in the body’s border, protecting us!

Scientific references:

1)Feingold, K.R., 2012. Lamellar bodies: the key to cutaneous barrier function. Journal of Investigative Dermatology, 132(8), pp.1951-1953.

2) Hänel, K.H., Cornelissen, C., Lüscher, B. and Baron, J.M., 2013. Cytokines and the skin barrier. International journal of molecular sciences, 14(4), pp.6720-6745.

3) Mahanty, S., Dakappa, S.S., Shariff, R., Patel, S., Swamy, M.M., Majumdar, A. and Setty, S.R.G., 2019. Keratinocyte differentiation promotes ER stress-dependent lysosome biogenesis. Cell death & disease, 10(4), p.269.

 4) Raposo, G. and Marks, M.S., 2007. Melanosomes—dark organelles enlighten endosomal membrane transport. Nature reviews Molecular cell biology, 8(10), pp.786-797.