Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin irritants and contact allergens reduce the number of Langerhans cells (LCs). It has been assumed that this reduction is due their migration to the draining lymph node (LN) for initiating immune sensitization in a host. Skin irritation, however, as opposed to contact allergy is not considered to be an immunological disease. Nevertheless, skin irritants are also known for their adjuvant-like effects on contact allergy, resulting in skin hypersensitivity reactions like toxic dermatitis. The human organotypic skin explant culture (hOSEC) model is used to study the characteristics of chemical-induced migration of CD1a(+) LCs out of the epidermis in relation to irritancy or toxicity. We analysed cells emigrating out of hOSEC for CD1a(+) LCs, CD83(+) mature dendritic cells (DCs) and CCR7(+) LN homing cells. After exposure to a toxic concentration of a non-immunogenic irritant, an increase of CD1a(+)CD83(+) LCs was found in the culture medium. A non-toxic concentration of an sensitizer induced an increase of CD1a(+) cells. About 50% of skin emigrating CD1a(+) LCs were CD83(-) (immature) but all were CCR7(+). Skin irritation by both non-allergenic and allergenic compounds induces LC migration and maturation. In contrast, only allergenic compounds induced LC migration with partial maturation at subtoxic concentration. This effectively demonstrates that irritation is physiologically needed stimuli for inducing LC maturation.
 ...
PMID:Skin irritants and contact sensitizers induce Langerhans cell migration and maturation at irritant concentration. 1668 59

Skin irritation is generally not considered to be an immunological event; however, alterations in the density of Langerhans cells (LC) in the epidermis do occur, which is indicative of LC migration. In this study, we investigated the migration of LC out of the epidermis after skin exposure to contact irritants and identified the chemokines involved. With the aid of ex vivo-intact human skin and epidermal sheets we show that dermal fibroblasts play a role in mediating LC migration towards the dermis. Exposure of ex vivo-intact human skin to a panel of seven irritants (SDS, salicylic acid, phenol, isopropanol, DMSO, TritonX, or benzalkonium chloride) resulted in decreased numbers of CD1a(+) cells in the epidermis and the accumulation of CD1a(+) cells in the dermis. In contrast to allergen exposure, neutralizing antibodies to either CXCL12 or CCL19/CCL21 did not inhibit LC migration out of the epidermis. Exposure of epidermal sheets to the prototypical irritant SDS resulted in a TNF-alpha-dependent LC migration towards dermal fibroblasts. This was a result of CCL2/MCP-1 and CCL5/RANTES chemokine secretion by fibroblasts: injection of CCL2- and CCL5-neutralizing antibodies into intact human skin totally inhibited LC migration into the dermis. We have thus identified a novel role for TNF-alpha-inducible dermis-derived CCL2 and CCL5 in initiating migration of irritant-exposed human LC out of the epidermis.
 ...
PMID:Epidermis-to-dermis migration of immature Langerhans cells upon topical irritant exposure is dependent on CCL2 and CCL5. 2043 37

Langerhans cells (LCs) have been the subject of much research since their discovery in 1868. LCs belong to the subset of leucocytes called dendritic cells. They are present in the epidermis and the pilosebaceous apparatus and monitor the cutaneous environment for changes in homeostasis. During embryogenesis, a wave of yolk sac macrophages seed the fetal skin. Then, fetal liver monocytes largely replace the yolk sac macrophages and comprise the majority of adult LCs. In the presence of skin irritation, LCs process antigen and travel to regional lymph nodes to present antigen to reactive T lymphocytes. Changes in LCs' surface markers during the journey occur under the influence of cytokines. The difference in expression of surface markers and the ability to resist radiation have allowed researchers to differentiate LCs from the murine Langerin-positive dermal dendritic cells. Exciting discoveries have been made recently regarding their role in inflammatory skin diseases, cancer and HIV. New research has shown that antibodies blocking CD1a appear to mitigate inflammation in contact hypersensitivity reactions and psoriasis. While it has been established that LCs have the potential to induce effector cells of the adaptive immune system to counter oncogenesis, recent studies have demonstrated that LCs coordinate with natural killer cells to impair development of squamous cell carcinoma caused by chemical carcinogens. However, LCs may also physiologically suppress T cells and permit keratinocyte transformation and tumorigenesis. Although long known to play a primary role in the progression of HIV infection, it is now understood that LCs also possess the ability to restrict the progression of the disease. There is a pressing need to discover more about how these cells affect various aspects of health and disease; new information gathered thus far seems promising and exciting.
 ...
PMID:Langerhans cell: exciting developments in health and disease. 2883 2