The skin is the body’s primary barrier against physical insults and microbial pathogens.
It represents a unique environment in which immune cells interact with skin cells to maintain tissue homeostasis and induce immune responses.
The skin is composed of epidermis, dermis, and a subcutaneous fatty region.
Commensal bacteria, fungi and viruses living on the skin have beneficial effects in the protection against pathogens and in wound healing.
The epidermis is composed of highly specialized epithelial cells known as keratinocytes.
They are continuously replenished from just one layer of basal keratinocytes which divide frequently.
Dead cells called corneocytes form the outer most layer and are largely responsible for the barrier function of the skin.
In the dermis, cells known as fibroblasts secrete elastin and collagen fibers that form a dense extracellular matrices.
Blood capillaries irrigate the dermis while lymph fluid is drained through lymphatic vessels to lymph nodes specialized immune structures in which immune cells are activated after pathogen encounter.
Diverse and functionally specialized immune cells populate the skin.
In the epidermis, a specialized subset of dendritic cells called langerhans cells sample antigen.
They project dendrites upwards toward the cornified epithelial layer and sample bacterial antigens such as toxins.
Langerhans cells appear to be both anti-inflammatory and activatory depending on contexts.
Dendritic cells in the dermis are highly efficient to capturing dead cells and presenting antigen such as viruses, other intracellular pathogens or skin associated self-antigen to T cells.
If dendritic cells are the immune sentinels, T cells are the immune effectors.
Healthy skin contains more than twice the number of T cells found in the blood.
Most of them are memory T cells that have previously encountered antigen and can be rapidly activated.
T cells in the epidermis are mostly CD8+ T cells, the subsets that become cytotoxic and kill target cells upon activation.
They’re long term residents in the epidermis, mostly disconnected from the circulation.
T cells in the dermis are mostly helper CD4+ T cells which have a more modulatory role in the immune response.
A variety of other immune cells such as natural killer cells, eosinophils and mast cells are present in the dermis and might be involved in a logic reactions in the skin.
Dendritic cells and keratinocytes sense tissue damage such as wounds or cuts or lesions that occur when latent herpes virus reactivates and they do that through evolutionarily conserved receptors that recognize pathogen-derived molecular patterns or host-derived molecules that are exposed by cell death such as DNA.
Keratinocytes produce antimicrobial peptides which can kill bacteria directly, inflammatory mediators such as interleukin one or IL-1 which activate dendritic cells and chemokines which recruits neutrophils, macrophages and T cells.
Activated dendritic cells migrate to the lymph nodes where they present antigens from the sight of infections to naive T cells, priming them to activate and differentiate into effective T cells.
Activated T cells returns to the skin and kill infected keratinocytes to control viral infection, also secrete signals that recruit additional immune affected cells.
Following viral clearance, memory CD8+ T cells persist in the epidermis to provide immunity for future encounters with the same virus.
Immune responses can become dysregulated and cause skin disorders such as psoriasis or atopic dermatitis.
Psoriasis is a lifelong inflammatory skin disease characterized by scaly reddish plaques, a combination of an environmental and genetic factors confer sustainability to the disease.
Physical injury or inflammation can trigger the formation of an acute lesion.
The antigenic trigger is unknown but current models propose that stressed keratinocytes might release self-DNA which in complex with an antimicrobial peptide activates dermal plasmacytoid dendritic cells to secrete high amounts of the antiviral mediator interferon.
Together with pro-inflammatory IL-1 alpha released by stressed keratinocytes interferon activates dermal dendritic cells to promote T cell differentiation.
The earliest recognizable change in the effective skin is the accumulation of T cells and dendritic cells around blood vessels in the dermis.
An overt legion occurs when CD8+ T cells, dendritic cells and neutrophils infiltrate the epidermis.
Specialized subsets of T cells secrete soluble mediators like interferon gamma and IL-17 which stimulates the proliferation of keratinocytes and this produces a marked thickening of the epidermis.
Signals from the proliferating keratinocytes acts as chemo-attractants for infiltrating neutrophils.
Crosstalk between immune cells, keratinocytes, and dermal cells thus contributes to tissue remodeling and amplification of dysregulated immune response.
Without treatment, acute psoriatic lesions become chronic lesions.
Genetic studies have identified psoriasis associated sustainability genes.
Some of them linking Th-17 cells, the subset of T cells that produce IL-17 to psoriasis pathogenesis.
Thus, immune cells in the skin exert important roles in maintaining the barrier function against pathogens but can also become activated by self-antigen or harmless antigen to cause autoimmunity or allergies.