Chapters authored
Pathogenic Role of Cytokines and Effect of Their Inhibition in Psoriasis
The pathogenesis of psoriasis is complex, and cytokines play an important role in mediating cell-cell interactions that result in abnormal structures and functions of many cell types in psoriasis, such as abnormal proliferation and differentiation of keratinocytes, abnormal proliferation of blood vessels, stimulation of immune cells, and driving abnormal immune reactions. In this chapter, we summarize the roles and functions of inflammatory cytokines that play a crucial role in psoriasis such as tumor necrosis factor (TNF)-α, interleukin (IL)-12/IL-23, and IL-17, as well as their inhibitors that are used to treat psoriasis.
Part of the book: Psoriasis
Keratinocyte Stem Cells: Role in Aging
Stem cells located in the skin are responsible for continual regeneration, wound healing, and differentiation of different cell lineages of the skin. The three main locations of skin stem cells are the epidermis, dermis, and hair follicles. The keratinocyte stem cells are located in the epidermal basal layer (the interfollicular stem cells), hair follicle bulge region (the hair follicle stem cells), and sebaceous glands (the sebaceous gland stem cells) and are responsible for the epidermal proliferation, differentiation, and apoptosis. The interfollicular (IF) stem cells are responsible for epidermis regeneration by proliferating basal cells that attach to the underlying basement membrane and with time they exit from the cell cycle, start terminal differentiation, and move upward to form the spinous, the granular, and the stratum corneum layers. The hair follicle (HF) stem cells are responsible for hair regeneration and these stem cells undergo a cycle consists three stages; growth cycles (anagen), degeneration (catagen), and relative resting phase (telogen). The sebaceous gland (SG) stem cells located in between the hair follicle bulge and the gland and are responsible for producing the entire sebaceous gland which secretes oils to moisture our skin. The role of epidermal stem cells is extremely crucial because they produce enormous numbers of keratinocytes over a lifetime to maintain epidermal homeostasis. However, the age-associated changes in the skin; for example; alopecia, reduced hair density, gray or thin hair, reduced wound healing capacity are related to skin stem cells’ decline functionality with age.
Part of the book: Keratinocyte Biology
Keratinocytes in Skin Disorders: The Importance of Keratinocytes as a Barrier
Keratinocytes are the major structural component of the epidermis. They differentiate from the basal through spinous to granular layers, and abrupt loss of nucleus pushes them to differentiate into cornified layers, which exfoliates as scales. Differentiation process is tightly controlled by the organized expression of transcription factors and other regulators, which sustains the physiological function of the skin barrier. The genetic abnormality of the molecules expressed in this pathway causes hereditary skin disorders and defects in barrier function. Ichthyosis is caused by keratins, enzymes, and structural proteins involved in lipid metabolism and cornified envelope formation. Atopic dermatitis seemed to be an immune-oriented disease, but the recent finding revealed filaggrin as a causative factor. Keratinocytes respond to acute injury by releasing alarmins. IL-33 is one of such alarmins, which provoke Th2-type inflammation. IL-33 works as a cytokine and, at the same time, as nuclear protein. IL-33 has double-faced nature, with pro- and anti-inflammatory functions. Epidermis, covering the entire body, should stay silent at minor insults, while it should provoke inflammatory signals at emergency. IL-33 and other double-faced molecules may play a role in fine tuning the complexed function of epidermal keratinocytes to maintain the homeostasis of human body.
Part of the book: Keratinocyte Biology