vasoactive-intestinal-peptide and Alopecia-Areata

Alopecia areata (AA) is an autoimmune disorder whose pathogenesis involves the collapse of the relative immune privilege (IP) of the hair follicle (HF). Given that vasoactive intestinal peptide (VIP) is an immunoinhibitory neuropeptide released by perifollicular sensory nerve fibres, which play a role in IP maintenance, it may modulate human HF-IP and thus be therapeutically relevant for AA.. To answer the following questions: Do human HFs express VIP receptors, and does their stimulation protect from or restore experimentally induced HF-IP collapse? Is VIP signalling defective in AA HFs?. Firstly, VIP and VIP receptor (VPAC1, VPAC2) expression in human scalp HFs and AA skin was assessed. In HF organ culture, we then explored whether VIP treatment can restore and/or protect from interferon-γ-induced HF-IP collapse, assessing the expression of the key IP markers by quantitative (immuno-)histomorphometry.. Here we provide the first evidence that VIP receptors are expressed in the epithelium of healthy human HFs at the gene and protein level. Furthermore, VIP receptor protein expression, but not VIP(+) nerve fibres, is significantly downregulated in lesional hair bulbs of patients with AA, suggesting defects in VIP receptor-mediated signalling. Moreover, we show that VIP protects the HF from experimentally induced IP collapse in vitro, but does not fully restore it once collapsed.. These pilot data suggest that insufficient VIP receptor-mediated signalling may contribute to impairing HF-IP in patients with AA, and that VIP is a promising candidate 'HF-IP guardian' that may be therapeutically exploited to inhibit the progression of AA lesions.

Topics: Alopecia Areata; Epithelium; Female; Hair Follicle; Healthy Volunteers; Humans; Interferon-gamma; Pilot Projects; Receptors, Vasoactive Intestinal Peptide, Type II; Receptors, Vasoactive Intestinal Polypeptide, Type I; RNA, Messenger; Scalp; Self Tolerance; Vasoactive Intestinal Peptide

Alopecia areata (AA) is a dermatosis involving the sudden occurrence of bald patches on the scalp. Although the aetiology is unknown, experimental data indicate that cutaneous microcirculation plays an important role. The skin is richly innervated by neuropeptidergic sensory nerves that help regulate microvascular circulation. This study shows a reduction of cutaneous levels of substance P and calcitonin gene-related peptide (CGRP) but not of vasoactive intestinal polypeptide in scalp biopsies from patients with AA. Laser-Doppler flowmetry was used to study microcirculation of the scalp. Results indicate that patients with AA have lower basal blood flow and greater vasodilatation following intradermal CGRP injection than control subjects. A vascular hyper-reactivity to vasodilatatory substances such as neuropeptides, probably because of the lack of these substances, is hypothesized.

Topics: Adolescent; Adult; Alopecia Areata; Biopsy; Calcitonin Gene-Related Peptide; Case-Control Studies; Humans; Injections, Subcutaneous; Laser-Doppler Flowmetry; Microcirculation; Middle Aged; Neurons, Afferent; Neuropeptides; Radioimmunoassay; Scalp; Sensation Disorders; Substance P; Vasoactive Intestinal Peptide