The role of Langerhans cells in epidermal homeostasis and pathogenesis of psoriasis

Abstract

The skin is the main barrier between the human body and the outside world, which not only plays the role of a physical barrier but also functions as the first line of defence of immunology. Langerhans cells (LCs), as dendritic cells (DC) that play an important role in the immune system, are mainly distributed in the epidermis. This review focuses on the role of these epidermal LCs in regulating skin threats (such as microorganisms, ultraviolet radiation and allergens), especially psoriasis. Since human and mouse skin DC subsets share common ontogenetic characteristics, we can further explore the role of LCs in psoriatic inflammation.

Keywords: Langerhans cells; epidermal homeostasis; inflammatory responses; psoriasis.

FIGURE 1

Occurrence and development of Langerhans cells (LCs). LCs are mainly differentiated from primordial erythrocytes‐myeloid progenitors (EMPs) in the yolk sac. There are three pathways to induce and migrate LCs to the epidermis. The development of LCs in the epidermis depends on CSF‐1R, a molecule which could maintain skin homeostasis through combining with IL‐34. LCs could be replaced by mononuclear progenitors, which could bind to CSF‐1, derived from bone marrow during inflammation

FIGURE 2

The role of Langerhans cells (LCs) in the occurrence and development of psoriasis. KCs stimulated by stress stimulation (such as cytokines) can stimulate the self‐nucleotide and antimicrobial peptide LL‐37 complex to activate epidermal LCs, inducing keratinocytes to specifically produce a variety of cytokines to promote the migration of LCs to lymph nodes (DLNs) and T‐cell activation. LCs can also activate the LIGHT‐LT β R signal axis to activate the expression of CCL21/CCL19 in DLN. At the same time, epidermal LCs can produce IL‐2, IL‐23 and TLR2. Among them, IL‐2 can promote the proliferation of Treg cells; TLR2 signal mediates the activation of the transcription factor NF‐κB, promotes LC maturation and migration to lymph nodes and induces Th17 differentiation. The cytokines produced by LCs promote Th17 and Th22 to activate the expression of IL‐17, IL‐22 and TNF‐α and promote the proliferation of keratinocytes and other features of psoriasis. Proliferated KCs once again release cytokines, antimicrobial peptides and chemokines to infiltrate immune cells, further enhancing the role of activated T cells and forming a positive feedback loop between psoriatic epidermal cells and the immune system

FIGURE 3

The three kinds of way to establish Psoriasis‐like Mouse Model. The first type of psoriasis‐like mouse model was intradermal injection of 500 mg of IL‐23 every other day for 15 days; the second kind was to smear 62.5 mg of imiquimod on the back every day for 6 days; and the third kind was intraperitoneal injection of tamoxifen for three consecutive days of 1 mg in DKO* mice, which could lead to acanthosis, incomplete keratosis and mixed inflammatory infiltration after 14 days