γδ T cells and inflammatory skin diseases

Abstract

γδ and αβ T cells develop in the thymus from common progenitor cells. 1 Unlike αβ T cells, the majority of murine γδ T cells are functionally committed during intra-thymic differentiation. 2-4 This underlines the importance of the thymic microenvironment in the regulation of the peripheral effector functions of γδ T cells. Central to the thymic microenvironment is the thymic epithelial cells (TEC), divided into cortical TEC (cTEC) and medullary TEC (mTEC). 5 Particularly, the mTEC seem to regulate the functional commitment of γδ T cells within the thymus. Recently, it has become clear that TEC, especially mTEC, are more heterogeneous than previously assumed. Interestingly, subsets of mTEC with expression profiles such as tuft cells and keratinocytes (KC) have been identified. 6,7 KC constitute the majority of cells within the outermost layer of the skin, the epidermis. The epidermis acts as our first line of defense against assaults from pathogens, chemicals, and allergens, thereby playing a critical role in providing protection from injury. Although KC are not classified as immune cells, they play important immunological roles in the first line of defense against pathogens and allergens. Thus, KC express pattern recognition receptors such as Toll-like receptors (TLR) 8 and NOD-like receptors (NLR), 9 some constitutively and others following stimulation, that are able to recognize pathogen-associated molecular patterns and damage-associated molecular patterns, which trigger the production and release of cytokines, chemokines, and anti-microbial peptides that in turn activate immune cells in the skin. 10-12 The immune cells found in the epidermis are T cells and a subset of antigen-presenting cells termed Langerhans cells (LC). 10,12,13 In naïve mice, the primary subset of T cells in the epidermis is a special subset of γδ T cells called dendritic epidermal T cells (DETC) due to their dendritic morphology. 14

Allergic Contact Cell-Mediated Hypersensitivity in Psoriasis: A Narrative Minireview

“…Because psoriasis alters the skin’s protective barrier, different microbes, irritants, and contact haptens/allergens more easily penetrate the cutaneous layer with presentation to dendritic cells. Therefore, allergic contact hypersensitivity has been reported as a possible comorbidity in psoriasis patients [ 1 , 2 , 3 , 13 ].…”

“…It affects all age groups, and its prevalence in the general population varies from 1% to 3%, with differences in various geographical areas due to environmental and genetic factors. Allergic contact dermatitis is caused by contact cell-mediated hypersensitivity and has a prevalence of about 15–20% in the general population [ 1 , 2 , 3 ]. This type IV hypersensitivity may be assessed in vivo with skin patch testing in selected patients with psoriasis and may be treated with either refractory or topical treatments, or with biologics if the patient is presenting with cutaneous lesions clinically suggestive of contact dermatitis.…”

D-Mannose Suppresses γδ T Cells and Alleviates Murine Psoriasis

“…Among the adaptive effector cells, T cells play an essential role in the pathology of skin disorders by activating keratinocytes through the IL-23/IL-17 axis (11,12). Conventionally, TCRab + Th cells have received plentiful attentions, but increasing evidences have shown that IL-17-secreting TCRgd + (gd17) T cells are pivotal mediators in psoriasis (13)(14)(15). In both IL-23-induced and imiquimod (IMQ)-induced models, gd T cell deletion rather than ab T cell deletion alleviated skin inflammations (16).…”

IgG from Adult Atopic Dermatitis (AD) Patients Induces Nonatopic Neonatal Thymic Gamma–Delta T Cells (γδT) to Acquire IL-22/IL-17 Secretion Profile with Skin-Homing Properties and Epigenetic Implications Mediated by miRNA

“…These cells express T-cell receptors composed of γ and δ chains (γδTCRs), and their ligands are still unknown, as recently discussed [ 2 , 3 , 4 , 5 ]. γδT cells can mediate the human atopic state [ 6 , 7 , 8 ], and some researchers suggest that they are involved in the development of atopic dermatitis (AD) [ 9 , 10 , 11 , 12 ]. Because of the functional plasticity of γδT cells, which are typically divided into IL-17- and IFN-γ-producing γδT cells, γδT cells can also produce other cytokines with modulatory effects, such as IL-22 [ 13 ].…”