Immunological mechanisms of contact hypersensitivity in mice

Abstract

Contact hypersensitivity (CHS) is an animal model in which the immunological mechanisms of allergic contact dermatitis (ACD) in humans can be studied but is also widely used in the study of many basic immunological mechanisms. In CHS, a pre-sensitized animal is re-exposed to an antigen, thereby eliciting an immunological reaction at the site of antigen exposure. CHS consists of two phases: sensitization and elicitation phase. In the sensitization phase, the first contact of the skin with a hapten leads to binding of the hapten to an endogenous protein in the skin where they form hapten-carrier complexes which are immunogenic. The hapten-carrier complex is taken up by Langerhans cells (LCs) and dermal dendritic cells (dDCs) which migrate from the epidermis to the draining lymph node. Here, they present the haptenated peptides to naive T cells which are subsequently activated. The newly activated T cells proliferate and migrate out of the lymph node and into circulation. In the elicitation phase, re-exposure of the skin to the hapten activates the specific T cells in the dermis and triggers the inflammatory process responsible for the cutaneous lesions. Originally CHS was regarded as being solely driven by T cells but recently other cell types such as B1 cells, natural killer (NK) T cells and NK cells have shown to mediate important functions during the response as well. Here, we have described the molecular and cellular pathways in the development of CHS and have focused on recent advances and novel knowledge in the understanding of the immunoregulatory mechanisms involved in CHS.

Suppression of antigen-specific adaptive immunity by IL-37 via induction of tolerogenic dendritic cells

“…Upon antigen uptake, DCs increase the expression of the chemokine receptor CCR7, which directs DCs to CCR7 ligands CCL19 and CCL21 expressed in dLNs (17)(18)(19). Similar to those from WT mice, BMDCs from IL-37tg mice upregulated CCR7 expression (Fig.…”

“…Skin DCs initiate CHS by capturing antigens, migrating to draining lymph nodes (dLNs), and priming naive T cells (17)(18)(19). Because cytokines and chemokines can alter development and localization of DCs (20,21), we examined the distribution of skin DCs in IL-37tg mice.…”

“…Murine contact hypersensitivity (CHS) is a DC-dependent inflammation mediated by hapten-specific T cells and a useful model to investigate delayedtype hypersensitivity (17)(18)(19). In the present study, we investigated the role of IL-37 in DCs and subsequent development of antigenspecific CHS responses using IL-37tg mice.…”

Sphingolipids and Inflammatory Diseases of the Skin

“…The most prominent DC subtypes in the skin are the Langerhans cells (LCs) (Christensen and Haase 2012;Kaplan 2010). They ferret out exogenous molecules that have penetrated the skin barrier and convey this information to the dermal lymph nodes.…”

Effect of the Hot Water Extract of <i>Artocarpus camansi</i> Leaves on 2,4,6-Trinitrochlorobenzene (TNCB)-Induced Contact Hypersensitivity in Mice

“…It provides the option of studying many aspects of the immune system and basic immunological mechanisms in vivo, which is relevant not only for ACD but for a whole range of inflammatory diseases. 3) Glucocorticoids are the more common treatment for ACD but they have high level of undesirable effects. Most patients especially in developing countries, like the Philippines, still resort to Complementary and Alternative Medicine (CAM).…”