Skin structure: how is it composed?

True interface between the organism and the outside world, the skin has many functions: it regulates temperature, perceives sensory stimuli and participates in the synthesis of certain vitamins and hormones. This complexity relies on a well-defined organization, composed of three distinct layers that work in synergy to ensure protection, regeneration, and proper skin function. The epidermis, the most superficial layer, provides defense against external aggressions and limits water loss. Just below, the dermis houses an extracellular matrix rich in supportive fibers, along with vascular, neural, and glandular networks. Finally, the hypodermis, the deepest layer, contains adipose tissue that cushions impacts and contributes to thermal insulation.

The epidermis forms the outermost layer of the skin and constitutes the first barrier between the organism and the external environment. Thin and semi-permeable, it protects against dehydration, pathogens, allergens, and UV radiation. Its composition is predominantly cellular: about 80% keratinocytes, supplemented by melanocytes, Langerhans cells, and Merkel cells. Devoid of blood and lymphatic vessels, the epidermis is nourished by diffusion from the dermis. It exhibits a highly variable thickness depending on the body region and continuously renews itself, thereby maintaining its integrity and protective function.

The epidermis is composed of five superimposed layers, from the deepest to the most superficial: the basal layer, the spinous layer, the granular layer, the clear layer, and the stratum corneum.

• The basal layer : Adjacent to the basement membrane, the basal layer houses the stem keratinocytes, cells that are actively dividing. They continuously generate new keratinocytes that migrate toward the surface. It is also in this layer that the melanocytes, responsible for melanin synthesis, and the Merkel cells, which are sensitive to pressure and touch, are found.

• The spinous layer : Composed of keratinocytes linked by desmosomes, this layer provides cohesion to the epidermis. It is also at this level that Langerhans cells, immune sentinels capable of capturing and presenting antigens to lymphocytes—a type of white blood cell—are located.

• The granular layer : It contains flattened keratinocytes harboring keratohyalin granules and lipid-rich lamellar bodies, essential for forming the skin barrier.

• The clear layer : Present only in the palms of the hands and the soles of the feet, this layer is composed of dead cells containing eleidin, a translucent derivative of keratohyalin.

• The stratum corneum : The stratum corneum consists of anucleate corneocytes—cells that have lost their nuclei—rich in keratin and embedded in a lipid matrix. This outermost layer provides the skin’s primary barrier function, limiting water loss while protecting it from external aggressors.

Between the epidermis and the dermis lies the basement membrane, serving as both an anchor and a communication interface. Composed of laminin, type IV and VII collagen, perlecan—a proteoglycan—and nidogen, a glycoprotein that links laminin to collagen, it provides the cohesion between the two skin layers while allowing the exchange of nutrients, oxygen, and molecular signals. The basement membrane also supports the hemidesmosomes of basal keratinocytes, which tightly attach the epidermis to the dermis.

The dermis is the skin’s middle layer, located between the epidermis and the hypodermis. Thick, elastic, and highly vascularized, it forms a complex connective tissue whose main role is to mechanically and functionally support the epidermis. The dermis also regulates body temperature, nourishes epidermal cells, supports wound healing, and enables sensory perception through a dense network of blood vessels, nerve endings, and sensory receptors. Its thickness varies across different body regions, and it represents the skin’s largest reservoir of water, thereby contributing to its flexibility and resilience.

The dermis is divided into two distinct regions: the superficial papillary dermis and the deeper reticular dermis.

• The papillary dermis : Located just below the dermo-epidermal junction, the papillary dermis consists of a loose connective tissue made up of fine collagen and elastin fibers and an extracellular matrix rich in glycosaminoglycans. It forms small projections called dermal papillae that interlock with the epidermis and facilitate nutrient exchange. These structures, particularly prominent on the fingers and soles of the feet, give rise to fingerprints. Highly vascularized and rich in sensory receptors, the papillary dermis contributes to the perception of touch, temperature, and vibration.

• The reticular dermis : Thicker, the reticular dermis forms the deep layer of the dermis. It consists of dense connective tissue made up of interwoven bundles of fibers of collagen and elastin that give skin its strength, elasticity, and extensibility. The main cells of the dermis are fibroblasts, the true architects of the extracellular matrix: they synthesize collagen, elastin, fibronectin, and proteoglycans, such as hyaluronic acid, essential to the hydration and viscosity of the skin tissue. The reticular dermis also houses hair follicles, sebaceous glands and sweat glands, as well as an extensive network of lymphatic and blood vessels, ensuring thermal regulation and immune defense.

The dermis is a key compartment from an immunological standpoint.

Indeed, the dermis contains the majority of cutaneous immunocompetent cells : macrophages, mast cells, dendritic cells, eosinophils, neutrophils, and T and B lymphocytes, including regulatory T cells and natural killer cells. These cells form a complex network of immune surveillance, capable of detecting any pathogen or local imbalance. In the event of a microbial attack, they release inflammatory mediators that recruit additional defense cells and orchestrate an appropriate immune response. This defense system is not limited to fighting infections: it also contributes to the maintenance of skin homeostasis and to tissue repair after injury, by stimulating fibroblast proliferation and the production of collagen to restore the dermal structure.

The hypodermis is the deepest layer of the skin. Located beneath the dermis, it connects the skin to deeper structures such as muscles, tendons, and bones. This loose connective tissue is richly vascularized and traversed by large blood vessels and nerves, ensuring metabolic exchanges between the skin and internal organs. The hypodermis provides support, protection, and energy storage, constituting both a mechanical shock absorber and a thermal regulator for the entire organism.

Its structure is primarily based on white adipose tissue, composed of adipocytes, fibroblasts, and cells of the vasculo-stromal compartment. The latter contains mesenchymal stem cells, endothelial cells, and immune cells such as T lymphocytes and macrophages. Mature adipocytes store energy in the form of large lipid droplets, which serve as a mobilizable metabolic reserve when needed. This energy storage also contributes to thermoregulation, as subcutaneous fat acts as a thermal insulator.

In addition to its mechanical and energy-storing functions, the hypodermis also stands out for its endocrine role. Indeed, adipocytes secrete a wide array of hormones and bioactive mediators—such as leptin, adiponectin, and certain cytokines—that contribute to the regulation of food intake, blood glucose levels, inflammation, and hair follicle growth. The composition of the hypodermis varies among individuals and body regions: it is thicker over the hips, buttocks, and abdomen, and thinner over the eyelids and forehead.

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