KERATINOCYTES: FUNCTIONS, HISTOLOGY, TYPES - BIOLOGY - 2025

The keratinocytes are a type of keratin producing cells which form much of the skin in mammals. In their different states of differentiation, keratinocytes can make up up to 90% of the epidermis.

Keratinocytes are important producers of cytokines, which are important proteins for intercellular communication processes.

Staining of the epidermis and the keratinocytes that comprise it.

This production of cytokines by keratinocytes has multiple consequences on the migration of inflammatory cells, effects on the immune system, and on the differentiation and production of other keratinocytes.

Due to the important role of keratinocytes in the epidermis and in intracellular communication functions, these types of cells have attracted the attention of specialists who study cellular, immunological and skin disorder processes.

Keratinocytes are also a promising source of stem cells for developing human and animal tissues.

Studies with this type of cells have allowed scientific achievements such as the cloning of mice from mouse keratinocytes and the production of human pluripotent and multipotential cells.

Keratinocyte functions

Keratinocytes are found in various stages of differentiation in the epidermis and are responsible for forming tight junctions with nerves in the skin. They also keep the Langerhans cells in the epidermis and the lymphocytes in the dermis in place.

Apart from this connective function, keratinocytes participate in the function of the immune system. The skin is the first line of defense and keratinocytes are responsible for secreting molecules that stimulate inflammation in response to injury.

Thus, the main objective of these keratin-producing cells is to protect against the invasion of microbes, viruses, fungi and parasites. Additionally, keratinocytes function to protect against UV radiation, and to minimize the loss of heat, solutes, and water.

Importantly, keratinocytes are used to investigate various skin phenomena, including epidermal acidification, DNA degradation, fatty acid metabolism and transport, local immune responses, cell regeneration, stem cell differentiation, and the formation of tumors.

Histology

The skin is divided into three layers: the epidermis, the outermost layer of the skin; the dermis, directly below the epidermis; and a subcutaneous or fatty layer, under the dermis. The epidermis can be divided into sublayers:

• The basal lamina (the inner layer)
• The spiny cell layer
• The granule cell layer
• The lucid cloak
• The horny layer (the outer layer)

Lifecycle

The following is a general description of the life cycle of a keratinocyte. A keratinocyte can have two destinations:

1. Being a dividing cell and staying in the basal lamina.
2. Differentiate and migrate through the layers of the skin.

In the basal lamina, the keratinocytes are constantly dividing by mitosis, thus generating new basal keratinocytes. These can continue dividing to produce new keratinocytes.

Some of these cells will remain with their parents and continue to replenish the basal keratinocyte population. These cells are known as stem cells. However, the other keratinocytes will begin the process of cell differentiation.

Over time, these differentiating cells push themselves upward as the next generation of cells forms below them. Eventually, they are pushed into the next layer of skin to become prickly cells.

As more and more cells are manufactured in the basal layer, the newly formed spiny cells continue to be pushed upward and eventually reach the granular layer. Here, cells undergo a series of molecular events in which their organelles and cell nucleus are degraded.

After they have been displaced to the upper, highly keratinized layers, the keratinocytes become scales. The morphology of these squamous cells is flat, which facilitates their detachment as dead from the skin.

Depending on the region of the body, this life cycle can take about a month. Throughout life, the skin is renewed approximately a thousand times. Not all cells in the basal cell layer will end up in scales, as some are necessary to maintain the initial population of cells.

This skin renewal process is highly regulated, this in order to ensure that there is always an adequate number of cells in each stage of the process. Thus, a balance is maintained between the stem cells of keratinocytes and those destined to differentiate terminally.

In general, as long as there are approximately equal numbers of cells for both populations (basal and differentiated), this balance will be maintained.

Types of keratinocytes

Keratinocytes change in appearance from one layer of skin to the next. They start in the basal cell layer and migrate upward. Those in the lowest stratum, or layer, of the skin are generally the only ones that divide.

Above these basal cells, there are several layers of larger spiny cells that are held together by intercellular attachment points called desmosomes.

Each desmosome is made up of membrane proteins that allow cells to bond with each other. These proteins in turn are attached by anchoring to other proteins, forming a disk-shaped plate on the inner surface of the membrane.

The anchor proteins are linked by keratin filaments. These desmosomes appear under light microscopy as pointy cell membrane projections that give cells a spiny appearance.

Above the spiny cells are the granule cells. This cell layer forms an impermeable barrier and is the boundary layer that separates the internal, metabolically active layers from the extremely keratinized and dead outer layers of the skin.

Above the granule cells are the squamous cells. These flattened cells are highly keratinized, which means that they are extremely packed with keratin protein.

Both the scales and the outermost layer of the granule cells, just below the scales, are protected with layers of other cross-linked proteins.

Keratinocytes and cytokines

Apart from being the major constituent element of the largest organ in the body (the skin), keratinocytes are very important for their production of cytokines.

These cytokines produced by keratinocytes fulfill important and varied functions in the body.

One of them is the pro-inflammatory process. The regulation of these pro-inflammatory cytokines and their role in keratinocytes is well documented.

Among its effects are the stimulation of keratin production, the increase of the adherence of certain bacteria to keratinocytes and the protection of keratinocytes against programmed cell death.

Keratin produced by keratinocytes also plays an important immune role.

Some studies have shown that these keratins are involved in the formation of white blood cell lymphomas in the skin and in the suppression of the immune system.

Other important functions of keratin produced by keratinocytes include regulation of keratin production, regulation of keratinocyte proliferation, and keratinocyte differentiation.

Influence on the structure of the epidermis

The different layers of the epidermis are formed depending on the different states of differentiation of keratinocytes. In general we can speak of five layers in the epidermis:

Horny layer: it is formed by keratinocytes without a nucleus. It is considered to be a layer of dead cells that varies in size in different parts of the body.

Lucid cloak: it is located only on some parts of the body, such as the palms of the hands or the soles of the feet.

Granular layer: it is formed by rhomboidal cells that have granules of keratohyalin, a precursor of keratin and that gives the granular shape to this layer.

Spiny layer: it is made up of layers of keratinocytes of between 5 and 7 rows. Cells have polygonal shapes that have intercellular bridges that help their union with adjacent layers.

Basal layer: it is formed by rows of cylindrical keratinocytes and they create intercellular bridges. In this layer is the well-known pigment that gives the skin color and is known as melanin.

References

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5. Rheinwald J. Green H. Epidermal growth factor and the multiplication of cultured human epidermal keratinocytes. Nature. 1977; 265 (5593): 421-424.
6. Vogt M. et al. Genetically Modified Keratinocytes Transplanted to Wounds Reconstitute the Epidermis. Proceedings of the National Academy of Sciences of the United States of America. 1994; 91 (20): 9307-9311.