1.2.7.1 Cells of the skin's immune system
The cells of the skin's immune system can be divided into professional immune cells and non-professional immune cells according to their functions.Professional immune cells include Langerhans cells，dendritic cells，lymphocytes，macrophages，and mast cells；nonprofessional cells include keratinocytes，fibroblasts，and endothelial cells（Table 1-1）.
Table 1-1 Distributions and functions of major immune cells in the skin
Continued
Keratinocytes are the first line of defense in the epidermal barrier.They play important roles in the early surveillance of pathogens by identifying viral nucleic acids，lipopolysaccharides，flagellin，and zymosan.At the same time，keratinocytes，like Langerhans cells，can ingest，process and present antigens to T cells，and can also release a variety of cytokines and chemokines，regulate immune responses and participate in inflammatory responses.Keratinocytes express a variety of membrane molecules：①Adhesion molecules，including intercellular adhesion molecule-1（ICAM-1），lymphocyte functionassociated antigen-3（LFA-3），integrin α2 β1/α6 β4and cadherin（E-cadherin，P-cadherin），etc.The binding of integrin α5 β1 to the receptor can mediate endocytosis and kill pathogens；the combination of ICAM-1 and LFA-1 can induce immune cells to migrate to the epidermis，provide costimulatory signals，and regulate cell-cell interactions.②MHC molecules.In normal circumstances，keratinocytes mainly express MHC class Ⅰ molecules.In inflammatory conditions（e.g.，discoid lupus erythematosus，psoriasis，and eczema），the expression of MHC class Ⅰ and class Ⅱ molecules can be up-regulated and participate in adaptive immune responses.③Surface receptors，including a variety of cytokine receptors and pattern recognition receptors，which can monitor changes in the external environment and provide pro-inflammatory and chemotactic signals to immune cells when pathogens invade.In addition，keratinocytes can secrete a variety of immune effector molecules such as cytokines（IL-1，IL-6，IL-7，IL-17，IL-23，TNF-α，and TGF-β，etc.），chemokines（CXCL8，CCL17，and CCL20，etc.），and a variety of antimicrobial substances to participate in the inflammatory response and regulate the immune response.
Langerhans cells are dendritic non-pigmented cells derived from bone marrow，accounting for 3％-5％of epidermal cells.Langerhans cell membrane molecules include CDla，MHC class Ⅰ and class Ⅱ molecules，CD45 and CD45RO，integrins β1 andβ2，Langerin（i.e.，CD207，which is a marker of Langerhans cells that can induce the formation of Birbeck particles in Langerhans cells），chemokines body（e.g.，CCR6）.CD1a is highly expressed in immature Langerhans cells，while its expression in the mature and cultured Langerhans cells is significantly reduced.Langerhans cells can secrete a variety of cytokines（IL-1，IL-4，IL-6，IL-10，IL-15，and TNF-α，etc.）and chemokines，such as macrophagederived chemokines，macrophage inflammatory protein-α，and monocyte chemoattractant protein-1，to mediate the homing of Langerhans cells from the peripheral blood to the skin and the migration from the epidermis to the dermal lymph nodes after ingesting antigens.Langerhans cells can regulate the proliferation and migration of T cells，and participate in immune regulation，immune surveillance，immune tolerance，skin graft rejection and contact hypersensitivity（see extended reading 4）.(https://www.daowen.com)
Skin dendritic cells include：①epidermal dendritic cells，that is，Langerhans cells（as described above）；②dermal-resident dendritic cells，which are dendritic cells that reside in the dermis，have the capacity of antigen-uptaking and presenting，the surface marker of which is CD1c；③“inflammatory”dermal dendritic cells，derived from circulating DC precursor cells，migrate to the skin under the stimulation of inflammation and chemokine signals，and the surface marker is CD11c+CDlc-，which can activate Th17 cells；④plasmacytoid dendritic cells（pDC），which are a special type of resident（skin）dendritic cells with a surface marker of BDCA-2，which can produce high levels of type 1 IFN during virus infection.The functions of skin DC include：①recognize PAMP（pathogen-associated molecular patterns）with the help of surface TLR（Toll-like receptor）and get activated，secreting TNF-α，etc.，to promote keratinocytes in contact with pathogens to produce TNF-α and IL-1；②activated dendritic cells migrate to the skin to drain lymph nodes initiating the adaptive immune response.
Macrophages include tissue colonized macrophages and macrophages derived from circulating monocytes infiltrating blood vessels into the skin to differentiate and develop.They can kill pathogens，phagocytosis of foreign bodies，senescent and degenerated tissue cells，and kill tumor cells，and it can be used as an antigen-presenting cell to participate in adaptive immune response.
Skin mast cells are mainly distributed around dermal blood vessels，hair follicles，nerves，and sebaceous glands.Mast cells not only participate in IgE-mediated type Ⅰhypersensitivity，but also play an important role in the anti-infective innate immunity and adaptive immune response，and participate in the occurrence of inflammatory autoimmune diseases.
The lymphocytes in the skin are mainly T cells，and the T cells in the epidermis account for about 2％of the total number of lymphocytes.Most of them are CD4+or CD8+T cells that express TCRαβ.The vast majority（over 90％）of T cells are located in the dermis，most of which are CD4+CD45RO+memory T cells，and the rest are CD8+T cells.The adhesion molecules involved in T cells homing are mainly skin lymphocyte-associated antigen（CLA）and E-selectin，as well as VLA-4，LFA-1 and ICAM-1/2（see extended reading 5）.