2.1.1.1 Composition of skin barrier
Skin barrier usually refers to the physical or mechanical barrier structure of epidermis，especially stratum corneum（Figure 2-1）.In terms of biochemical composition and function，the physical barrier structure of epidermis is related to the lipid of epidermis，and also to various proteins，water，inorganic salts and other metabolites.
1.Stratum corneum
Stratum corneum is mainly composed of keratinocytes and lipids.The extracellular lipids act as permeability，antioxidant，and antimicrobial barriers，and the keratinocytes act as ultraviolet and mechanical barriers.The stratum corneum is formed by differentiation and renewal of keratinocytes.During the cornification，keratinocytes undergo different developmental stages from cycling keratinocytes in the stratum basale，through early to late differentiating cells in the stratum spinosum and the stratum granulosum to dead keratinocytes in the stratum corneum.Keratin and keratin intermediate filaments-associated protein are involved in the process of cornification.
The keratinocytes develop a protein-and lipid-rich peripheral envelope，called the cornified envelope.In the outermost layer of the cornified envelope，ceramides and other lipids are covalently bound and form the so-called lipid envelope.The main function of the lipid envelope is to prevent trans-epidermal water loss（TEWL）and the loss of solutes，such as Na+、K+and Ca2+.
2.Desmosomes and tight junctions
Desmosomes seal the apical end of the lateral cell membrane and the extracellular fluid is compartmentalized into two parts by desmosomes maintaining different ionic strengths and solute concentrations.
In addition to desmosomes，tight junctions also contribute to the formation of the skin barrier.Tight junctions include a variety of transmembrane and intracellular proteins，mainly including Claudin family，Occludin family，ZO family，adhesion molecule family and so on.These proteins cross-link each other in the process of cell polarity and differentiation，and eventually form a dense network structure，blocking the intercellular space.Tight junctions are not just physical barriers；they exhibit ion and size selectivity and their barrier function varies significantly in tightness，depending on cell type and physiological requirements，enabling dynamic regulation of substances that traffic between compartments.(https://www.daowen.com)
3.Langerhans cells
Langerhans cells（LCs）play an important role as an immune barrier.They are antigenpresenting cells of the skin，which can recognize，bind and process antigens invading the skin and deliver them to T cells.When the body is in homeostasis，the dendrites of Langerhans cells are outwards，on the medial side of the tight junctions.When activated，dendrites of Langerhans cells cross the tight junction barrier and take up antigens from the outer environment.
4.Others
Keratinocytes synthesize and secrete diverse antimicrobial peptides（AMPs），which have antimicrobial properties.AMPs can interact with and bind to the lipid envelope and together provide the functions to kill or inactivate microorganisms when the microorganisms come into contact with the epidermis.There is an epidermal calcium ion gradient with low calcium ion concentrations in the basal，proliferating layers，and a progressively higher concentration as one proceeds to the outer differentiated layers.This epidermal calcium ion gradient plays a crucial role in skin barrier function.The epidermal calcium ion gradient regulates the epidermal differentiation process and the homeostasis of the epidermal permeability barrier.
Skin surface pH ranges from 4.5 to 5.5 in humans，which is slightly acidic compared to the normal physiologic pH.The acidity of stratum corneum is crucial for establishing the epidermal permeability barrier，as well as producing the epidermal antimicrobial barrier and controlling the integrity and cohesion of stratum corneum.Moreover，a lot of protein degrading enzymes and proteases exist in the stratum corneum and each protease has its optimal pH.
Protease also participates in the barrier function of epidermis.The continuous renewing process is balanced by shedding of the“old”keratinocytes from the surface of the epidermis，which is referred to desquamation.