Skin irritants and contact sensitizers induce Langerhans cell migration and maturation at irritant concentration

Abstract

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.

Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host

“…Proteolysis increases cellular mobility and inflammatory signals within the dermis and enhances interaction between immobilized virions and permissive cell types, such as Langerhans cells or macrophage (29). Irritant and allergen-dependent modulation of the dermal environment has previously been shown to induce migration of Langerhans cells to draining lymph nodes (29)(30)(31)(32). This is correlated with a fibroblast-and IL-10-dependent switch of Langerhans cells to a macrophage-like phenotype and may require the breakdown of integrin-mediated interactions with extracellular matrix components (32,33).…”

Phl p 5 resorption in human oral mucosa leads to dose-dependent and time-dependent allergen binding by oral mucosal Langerhans cells, attenuates their maturation, and enhances their migratory and TGF-β1 and IL-10–producing properties

“…27,28 Nevertheless, the accelerated migration in combination with the immature phenotype of oLCs after Phl p 5 binding remains in contrast with other investigations, which demonstrated that migrating DCs from skin are fully maturated. [29][30][31] Of course, this phenomenon might result from the culture condition used in our system. However, we demonstrated that LCs that migrated from epidermal sheets after allergen stimulation under the same culture conditions as in our mucosal model displayed high expression of the DC maturation marker CD83 and the DC homing factor CCR7 (data not shown).…”

MUTZ-3 Langerhans Cell maturation and CXCL12 independent migration in reconstructed human gingiva

“…With regards to skin, a number of in vitro models are available to investigate DC biology, in particular in the area of human safety and risk assessment of chemicals, and for testing novel drugs and therapeutic strategies (Roggen, 2014;dos Santos et al, 2009;Gibbs et al, 2013). Since large pieces of skin are regularly available from routine surgical procedures (e.g., abdominal dermolipectomy), fresh human skin explants provide a very relevant model to study Langerhans cell (LC) biology in situ (Ouwehand et al, 2008(Ouwehand et al, , 2010Jacobs et al, 2006;Lindenberg et al, 2013;Oosterhoff et al, 2013). Even so, the logistics around getting fresh tissue to the laboratory, the short viability of the tissue ex vivo (48 h) and the extremely limited size of oral mucosa (gingiva) biopsies, which are also often infected with microorganisms, provide profound limitations to implementing these tissues directly as a research tool.…”