As the body's largest organ, the skin mainly acts as a physical barrier.It is the first line of defense against infection and injury, protecting the body from potential attacks by exotic organisms or toxic substances.At the same time, it is essential for the regulation of temperature and humidity, substance metabolism, and so forth. The skin is also an interface with the external environment, and its sensory ability helps individuals to interact amicably with the environment. Because it is directly exposed to the environment, it is frequently damaged. For this reason, skin diseases are very common. Although most skin diseases are not life-threatening, they may affect the appearance and make those with skin conditions vulnerable to harmful psychological effects. Therefore, research on the pathogenesis of skin diseases has traditionally been the direction of researchers' efforts.Cell death mechanisms can be traditionally classified into two types: programmed cell death (PCD) mechanisms and necrotic cell death. For many years, apoptosis was thought to be the only form of PCD. Until in the last decade, evidence suggested that additional forms of PCD exist, such as necroptosis (programmed necrosis).Necroptosis is a genetically controlled process of cell death and shares common morphological features with multiple PCD, such as increased cellular volume, organelle swelling, and plasma membrane destruction. However, they are activated by different triggers and are executed by different signaling pathways. Apoptosis does not cause an immune response because no cellular material is discharged into the interstitial space and phagocytes do not release inflammatory cytokines. Unlike apoptosis, necroptosis can elicit a strong adaptive immune response. Necroptosis has become an important pathological process of various diseases. At the same time, it is considered to be the mechanism of inhibiting tumor progression in tumor biology.Many excellent studies have explored the signal transduction cascade, pathophysiological correlation, and clinical disease models, such as neurodegeneration, 1 cancer, 2 virus infection, 3 cardiovascular disease, 4 and therapeutic interventions involving necroptosis. In recent years, an

Skin photodamage includes sunburn, phototoxic dermatitis, photosensitive dermatitis and photoaging. These common skin diseases that affect appearance are caused by ultraviolet radiation. The ultraviolet rays that reach the Earth are mainly divided into longwave ultraviolet rays (ultraviolet radiation A, UVA, 320 ~ 400 nm) and medium-wave ultraviolet rays (ultraviolet radiation B, UVB, 290 ~ 320 nm). UVA accounts for 95% of the ultraviolet radiation that reaches the Earth's surface 1 and leads to skin ageing and wrinkling because of cellular DNA damage by reactive oxygen species (ROS) production. 2,3 UVB is a major cause of skin reddening and sunburn through direct DNA damage. 3 Therefore, both types of UV radiation are chief causes of skin damage and can induce skin inflammation, ageing and eventually skin cancer. Human keratinocytes, as the outermost barrier of the skin, are the main target cells of UV radiation. Studies have shown that UV irradiation can induce different forms of programmed cell death (PCD) in keratinocytes, including apoptosis, pyroptosis, necroptosis and autophagy (Figure 1). In this review, we will briefly introduce the various types of PCD and their roles in UV-induced skin photodamage. | AP OP TOS IS | Introduction to apoptosisApoptosis is type of cell death in which the cell membrane remains intact. Apoptosis essentially does not induce inflammatory reactions. Initiator caspases (mainly caspase-2, −8, −9 and −10) and executioner caspases (such as caspase-3, −6 and −7) participate in the process of apoptosis. Apoptosis controls the development and homeostasis of multicellular organisms, and the distinct morphological characteristics of apoptosis are cell shrinkage and pyknosis,

Background: Immune-related cutaneous diseases are a series of disorders, such as alopecia areata, psoriasis, atopic dermatitis, systemic lupus erythematosus and autoimmune bullous dermatoses. Vitamin D is a fat-soluble vitamin, which is known for its classical pleiotropic effect. Recent studies have found that vitamin D, after catalyzed into its biologically active form [1,25[OH] 2D], correlated with its receptor, vitamin D receptor, plays a vital role in multiple pathophysiological processes, including immune-related dermatoses. This review mainly summarizes evidence on the role of vitamin D/vitamin D receptor in immune-related cutaneous diseases and the potential therapeutic targets for skin disorders. Methods: We have carried out a comprehensive literature search in PubMed and Google Scholar databases using keywords like “vitamin D”, “vitamin D receptor”, “immune”, “psoriasis”, “atopic dermatitis”, “skin”, “systemic lupus erythematosus”, “alopecia areata” and “autoimmune bullous dermatoses”. Only articles related to the topic were included in this review. Conference, patent, graduation thesis and articles without available full text were excluded. Results: Vitamin D/vitamin D receptor is critical for skin in regulating the proliferation and differentiation of keratinocytes, keeping the integrity of the skin barrier as well as maintaining the homeostasis of the skin's immune system. Vitamin D deficiency/vitamin D receptor mutations are potential risk factors for some immune-related cutaneous diseases. Conclusion: Vitamin D is a pleiotropic hormone, which is important in the homeostasis of human body. Many studies have revealed vitamin D deficiency in several skin diseases. Thus, vitamin D supplementation may be a useful therapeutic option for immune-related skin diseases.