Keratinocytes: what are they, functions and developmental stages of these cells?

Keratinocytes are among the most common cells in the skin. Let's see what they look like.

The skin is the largest organ of the human body. With about two square meters of surface area and up to five kilograms of total weight, this tissue conglomerate is the most important primary Biological barrier of complex living beings, along with mucus, saliva, tears, sweat and certain behavioral mechanisms (such as coughing).

The skin is an inclement environment for pathogens because it is dry, has a slightly acidic pH, has antiseptic properties and, in addition, there are other microorganisms that already colonize this layer without causing us any harm (staphylococci, micrococci and Acinetobacter). All this makes it very difficult for bacteria and parasites that want to take advantage of us, because they encounter a physiological and living barrier that is practically impassable.

It is therefore not surprising to learn that the vast majority of skin infections begin with a wound: when a crack opens up in this wall, both commensal and pathogenic bacteria take advantage of the new, unprotected environments that open up beneath the lesion. After all, the innermost layers of our skin are irrigated and contain thousands of living cells: for a parasite, this is equivalent to unlimited nutrients.

Beyond functionalities, pathogens, physicochemical properties and immune mechanisms, to understand the nature of the skin we must turn to its most external and well-known part: the epidermis. In it, there is a very striking cellular group that dominates and defines the tissue. Let's see what keratinocytes are all about..

What are keratinocytes?

As we have said, keratinocytes are the most abundant cell type in the epidermis of human beings.. In our species, they account for 95% of the cell bodies of this layer, accompanied in much smaller proportion by melanocytes, Langerhans cells and Merkel cells.

As their name suggests, keratinocytes are in charge of synthesizing are in charge of synthesizing keratin and, in turn, give it the relevant properties to each of the four layers of the epidermisThe keratinocytes are the basal layer, the stratum spinosum, the stratum granulosum and the stratum corneum. As a curiosity, it is worth noting that the passage of a cell from the basal layer to the horny zone takes about 15 days, an extremely fast period if we look at the rate of tissue turnover in other parts of the body.

Characteristics of keratinocytes

First of all, it should be noted that this cell type has an ectodermal origin, i.e. it comes from the distal outermost layer of the fetus and is the first to develop.. They are a cell type that releases very little matrix and, therefore, the membranes of contiguous cells are tightly bound. This makes all the evolutionary sense in the world: the less space is left between the bricks of a wall, the more difficult it is for cracks to appear.

In addition to physical proximity, it is worth noting that between keratinocytes there are a series of junctions called desmosomes. This "bridge" is mediated by cadherins to a series of intermediate filaments (keratin), which allow the union between cells, thus giving the epidermis a very resistant cohesion and integrity over time.

The classical keratinocyte consists of 72-80% water, cytoplasm, organelles, nucleus and the expression of various types of keratin, depending on its location.depending on its location.

It should be noted at this point that keratinocytes do not have a specific shape throughout their life (which in humans is one month), since they pass through different epidermal layers and, therefore, must adapt to different functionalities. In order to show you what these cell bodies look like at each stage and layer, we must show you, even if only in broad strokes, what the process of keratinization consists of. Let's get down to it.

Keratinization in a nutshell

The terminal differentiation of keratinocytes from the stratum basale to the stratum corneum occurs under a process known as "keratinization.". We will see its particularities in a brief layer by layer manner.

1. Stratum basale

It is the first layer of the epidermis, in particular, the only one in which melanocytes are present, more or less at a rate of one for every 23 keratinocytes. This stratum is conceived as a real tissue factory, since it is formed by only one row of keratinocytes that are dividingin order to populate the following layers.

These keratinocytes are joined to the basal lamina (which separates the dermis from the epidermis) by hemidesmosome-type junctions, so that one cellular pole is clearly differentiated from the other. We do not want to go into histological particularities, but it is enough to know that this stratum contains adult epithelial stem cells, which give rise to keratinocytes. To give you an idea, there is usually one stem cell for every 3,500 keratinocytes in this layer.

2. Stratum spinosum

It originates from the mitotic division of the cells of the stratum basale, so it is immediately above it.. In this section, the keratinocytes adopt a polyhedral shape of about 15 micrometers in diameter, larger and more turgid than those present in the stratum basale. The name "spiny" comes from the desmosome and tonofibril-like junctions that connect the cells to each other.

It should be noted that, as they progress through the strata, keratinocytes express distinct cytoplasmic proteins of the keratin type. If in the stratum basale K5 and K14 dominated, here we find K1 and K10.

3. Stratum granulosum

In this layer an important event takes place in this layer: gene expression (the synthesis of substances (the synthesis of substances encoded by the nuclear DNA) of the keratinocytes changes. In the stratum granulosum, these cell types synthesize keratohyalin granules, basophilic compounds of irregular nature that occur in the cytoplasm of keratinocytes in this layer (hence the name). The typical keratin types of this phase are K2 and K11.

4. Stratum corneum

In the stratum corneum, the keratinocytes differentiate and degenerate, giving rise to corneocytes.. These have no nucleus or cytoplasmic organelles: they only have a thick membrane and multiple lipids, necessary for the structure. They are approximately 50 micrometers in diameter (larger than the rest) and are organized in columns of 10 to 30 units to form the stratum corneum proper.

It should be noted that, in addition to losing the nucleus and organelles, corneocytes do not retain more than 15% water by weight, compared to 70% of keratinocytes in the basement membrane. This gives the outermost layer of the epidermis its necessary dryness, which is very important for many microorganisms to be unable to colonize it.

Its relationship with the immune system

As you can see, one of the most striking functions of keratinocytes is to "die" to become impassable biological barriers, but this is not their only function.but this is not the only one of their essential tasks.

Notably, invasion by pathogens or contact with allergens in the epidermis brings out the "immune" side of keratinocytes. They produce a plethora of cytokines, proteins of a proinflammatory nature, such as interleukins (IL)-1, -6, -7, -8, -10, -12, -15, -18, and -20. These cytokines attract immune bodies such as monocytes or T lymphocytes to the site, which begin to act and/or divide in order to destroy the pathogenic agent.

This physiological basis is the basis for well-known pathologies such as contact dermatitis.. When the immune system recognizes a harmless allergen as harmful, lymphocytes travel to the skin surface and produce local responses, such as the characteristic itching, swelling and rash. Although it may not look like it, the immune system is fighting an unfounded pathogen.

Summary

As you have seen, keratinocytes have both a direct and indirect protective function. Not only are they structural "plugs" in their final phase due to their large size and low water content, but they are also capable of secreting substances that alert the immune system that something is wrong and trigger local reactions, for better and for worse.

Can you imagine what would have become of human beings without a series of mechanisms as effective as those described here? En un medio tridimensional en el que hasta el sol nos ataca, comprender la vida sin los queratinocitos y la epidermis sería una tarea imposible.

Referencias bibliográficas:

• Barker, J. N., Griffiths, C. E. M., Nickoloff, B. J., Mitra, R. S., & Dixit, V. M. (1991). Keratinocytes as initiators of inflammation. The Lancet, 337(8735), 211-214.
• Benhadou, F., Mintoff, D., & Del Marmol, V. (2019). Psoriasis: keratinocytes or immune cells–which is the trigger?. Dermatology, 235(2), 91-100.
• Cervellati, F., Benedusi, M., Manarini, F., Woodby, B., Russo, M., Valacchi, G., & Pietrogrande, M. C. (2020). Proinflammatory properties and oxidative effects of atmospheric particle components in human keratinocytes. Chemosphere, 240, 124746.
• Eckert, R. L., Crish, J. F., & Robinson, N. A. (1997). The epidermal keratinocyte as a model for the study of gene regulation and cell differentiation. Physiological reviews, 77(2), 397-424.
• Furue, M., Furue, K., Tsuji, G., & Nakahara, T. (2020). Interleukin-17A and keratinocytes in psoriasis. International journal of molecular sciences, 21(4), 1275.
• Oviedo Zegarra, C. A. (2019). Analysis of the use of keratin as a biomaterial.