Catecholamines Inhibit the Antigen-Presenting Capability of Epidermal Langerhans Cells

Abstract

The sympathetic nervous system modulates immune function at a number of levels. Within the epidermis, APCs (Langerhans cells (LC)) are frequently anatomically associated with peripheral nerves. Furthermore, some neuropeptides have been shown to regulate LC Ag-presenting function. We explored the expression of adrenergic receptors (AR) in murine LC and assessed their functional role on Ag presentation and modulation of cutaneous immune responses. Both purified LC and the LC-like cell lines XS52-4D and XS106 expressed mRNA for the ARs α1A and β2. XS106 cells and purified LC also expressed β1-AR mRNA. Treatment of murine epidermal cell preparations with epinephrine (EPI) or norepinephrine inhibited Ag presentation in vitro. Furthermore, pretreatment of epidermal cells with EPI or norepinephrine in vitro suppressed the ability of these cells to present Ag for elicitation of delayed-type hypersensitivity in previously immunized mice. This effect was blocked by use of the β2-adrenergic antagonist ICI 118,551 but not by the α-antagonist phentolamine. Local intradermal injection of EPI inhibited the induction of contact hypersensitivity to epicutaneously administered haptens. Surprisingly, injection of EPI at a distant site also suppressed induction of contact hypersensitivity. Thus, catecholamines may have both local and systemic effects. We conclude that specific ARs are expressed on LC and that signaling through these receptors can decrease epidermal immune reactions.

Pituitary adenylate cyclase‐activating polypeptide inhibits cutaneous immune function

“…Furthermore, PACAP potentiates acetylcholine-mediated catecholamine release [47]. Since catecholamines have been implicated in downregulating cutaneous immunity, this may be another mechanism by which PACAP exerts its effects [48].…”

“…The preparation of EC, eEC, and pLC is detailed in Seiffert et al [48]. Briefly, the epidermis was separated from dermis using 0.5 U dispase/ml (Boehringer, Indianapolis, IN) and 0.38% trypsin (Sigma) for 45 min, followed by scraping and dissociation of EC by mild agitation.…”

The Vesicular Monoamine Transporter 2 (VMAT2) Is Expressed by Normal and Tumor Cutaneous Mast Cells and Langerhans Cells of the Skin but Is Absent from Langerhans Cell Histiocytosis

“…VMAT2 expression in epidermal Langerhans cells suggests that these cells constitutively accumulate, store, and release monoamines. The physiological action of monoamines such as catecholamines on skin immune function is well documented (Maestroni 2000;Seiffert et al 2002;Kunzmann et al 2003;Mazzoni et al 2003). A few histochemical studies have demonstrated specific monoamine uptake in epidermal Langerhans cells Sjoborg et al 1978;Uno and Hanifin 1980;Crivellato et al 1990;Falck et al 1993).…”

Cathelicidin Antimicrobial Peptides Block Dendritic Cell TLR4 Activation and Allergic Contact Sensitization

“…Ear thickness was measured using a micrometer, (Mitutoyo) (18). For evaluation of the effect of excess cathelicidin, 0.04 ml of mCRAMP (GLL-33 aa peptide) in PBS (100 M) or PBS alone was injected intradermally.…”