Keratinocytes: Structure, Function & Diseases

Keratinocytes are horn-forming cells that make up the bulk of all cells in the epidermis (cuticle), accounting for more than 90 percent. They are proliferated at the basal layer of the epidermis and migrate from the basal layer to the surface of the skin during their approximately 28-day life with ongoing production of keratin. They give the skin strength by interlocking with each other and form a protective shield against external influences.

What are keratinocytes?

Keratinocytes derive their name from their ability to produce keratin or horny substance. They are formed continuously from basal stem cells located in the lowest layer of the epidermis, the stratum basale. As they are slowly pushed towards the skin surface by subsequent cells over the course of their approximately one-month life, they continue to produce keratin, also called horny substance, and undergo programmed cell death by dissolving their nucleus. Before reaching the skin surface, they form cell processes called desmosomes, with which they interlock to form a protective shield that gives the skin its firmness and protects it from the penetration of water, chemicals, pathological germs and UV rays. By the time they reach the skin’s surface, keratinocytes undergo ongoing changes in shape and cellular content. Just before the normal exfoliation process, which is ongoing, the cell completely loses its structure and cell membrane. It has evolved from a keratinocyte to a corneocyte, a horny cell. However, keratinocytes do not only play a passive role as a protective barrier, but are also involved in inflammatory processes, active defense against germs and in the wound healing process, and are thus part of the active immune system.

Anatomy and structure

Keratinocytes undergo constant changes in terms of shape and cell content during their relatively short existence. Immediately after their formation from mitotic cell divisions of epidermal stem cells in the basal layer of the epidermis, their differentiation into keratinocytes begins. They are fully equipped with nucleus, cytoplasm, enclosed cell organelles and vesicles and have a cylindrical shape. In the granular layer (stratum granulosum) lying immediately above the basal and prickle cell layers, the keratinization process and dissolution of the nucleus progress. Vesicles containing certain proteases empty their contents into the cytoplasm so that the nucleus and other cell contents are dissolved and metabolized. This is de facto a pre-programmed suicide of the cell. The cells flatten more and more and the cell interior is gradually filled by keratin globules, the keratin granules. Before the keratinocytes reach the outermost layer, the stratum corneum and the stratum disjunctim, they pass through the shiny layer, the stratum lucidum, which is either strongly or only slightly pronounced, depending on the body region. This is a thin boundary layer enriched with the special protein keratohyaling granules, which has a semi-fluid consistency and protects the skin from invaders and from dehydration.

Function and tasks

The tasks and functions of keratinocytes can be divided into mechanical-physical functions and biological-immunological functions. In the uppermost layer of the skin, the stratum corneum, keratinocytes bear their name with good reason. They can no longer react to messenger substances because they have lost their cell nucleus and also the multitude of their organelles. Before their exfoliation and “release” into the environment, the main task of the keratinocytes is to establish the mechanical tensile strength of the skin, which is well accomplished by the mutual interlocking of the cells. In addition, the keratinocytes prevent the penetration of water or other liquids or the penetration of solid substances in the form of dust or pathogenic germs. On the other hand, they also prevent the leakage of tissue fluid or unrestrained drying of the body due to the different vapor pressures between the body and the surrounding air. In their early stages, when keratinocytes still have an intact cytoplasm, they are part of the active immune response. They are capable of producing cytokines such as interleukins and chemokines. In particular, through the release of TNF-alpha (tumor necrosis factor) and IL-1, keratinocytes actively intervene in the immune response and in inflammatory processes.They thus mainly support the work of other cells of the immune system. The cytokines released when needed can also trigger systemic body reactions such as fever and other immune responses. Keratinocytes even provide some protection against harmful UV radiation because they can take up melanin-containing vesicles from melanocytes and use the melanin they contain to protect their nucleus.

Diseases

In addition to local inflammatory processes of the skin due to infections from injuries and local skin lesions, various skin cancers and systemic skin lesions such as psoriasis are considered to be the most important and common skin diseases. Basal cells, which constantly replenish keratinocytes through mitotic divisions, can develop a so-called basal cell carcinoma, a semi-malignant skin tumor that hardly metastasizes but can attack surrounding tissue such as bone and cartilage. Basal cell carcinoma is the most common type of skin cancer. Actinic keratosis is caused by local uncontrolled proliferation of keratinocytes, which usually manifests itself in reddish and rough skin patches. The disease represents an early form of spinalioma, the so-called prickle cell cancer, which develops as a malignant tumor in the prickle cell layer (stratum spinosum). Most often, the cancer occurs on the face in people over 70 years old. For people affected by psoriasis, the disease is not immediately threatening, but it can be very unpleasant due to the visible skin changes. Several parallel processes lead to a proliferation rate of the keratinocytes by a factor of four to seven. The cells can no longer differentiate in the short time available. In addition, immune system dysfunction most likely occurs.

Typical and common skin diseases

  • Vitiligo (white spot disease).
  • Skin rash
  • Skin fungus
  • Rosacea (rosacea)
  • Systemic lupus erythematosus (SLE)
  • Skin cancer