Abnormal interactions between perifollicular mast cells and CD8+ T-cells may contribute to the pathogenesis of alopecia areata.

Alopecia areata (AA) is a CD8+ T-cell dependent autoimmune disease of the hair follicle (HF) in which the collapse of HF immune privilege (IP) plays a key role. Mast cells (MCs) are crucial immunomodulatory cells implicated in the regulation of T cell-dependent immunity, IP, and hair growth. Therefore, we explored the role of MCs in AA pathogenesis, focusing on MC interactions with CD8+ T-cells in vivo, in both human and mouse skin with AA lesions.

The immune system of mouse vibrissae follicles: cellular composition and indications of immune privilege.

Although vibrissae hair follicles (VHFs) have long been a key research model in the life sciences, their immune system (IS) is essentially unknown. Therefore, we have characterized basic parameters of the VHF-IS of C57BL/6J mice by quantitative (immuno-)histomorphometry. Murine anagen VHF harbour few CD4+ and CD8+ T cells in the distal mesenchyme and sinuses but hardly any gamma-delta T cells in their distal epithelium.

Calcitonin gene-related peptide (CGRP) may award relative protection from interferon-γ-induced collapse of human hair follicle immune privilege.

Interferon-γ (IFNγ)-induced collapse of hair follicle (HF) immune privilege (IP) is a key element in the pathogenesis of alopecia areata. In this pilot study, we investigated whether the immunosuppressive neuropeptide, calcitonin gene-related peptide (CGRP), can protect from and/or restore IFNγ-induced HF-IP collapse. After showing that human scalp HFs express CGRP receptor-like receptor (CRLR) immunoreactivity, anagen HFs were cultured in the presence of IFNγ, with CGRP added before or after.

Genome-wide association study in alopecia areata implicates both innate and adaptive immunity.

Alopecia areata (AA) is among the most highly prevalent human autoimmune diseases, leading to disfiguring hair loss due to the collapse of immune privilege of the hair follicle and subsequent autoimmune attack. The genetic basis of AA is largely unknown. We undertook a genome-wide association study (GWAS) in a sample of 1,054 cases and 3,278 controls and identified 139 single nucleotide polymorphisms that are significantly associated with AA (P View Article and Find Full Text PDF

Thyroid-stimulating hormone, a novel, locally produced modulator of human epidermal functions, is regulated by thyrotropin-releasing hormone and thyroid hormones.

Several elements of the hypothalamic-pituitary-thyroid axis (HPT) reportedly are transcribed by human skin cell populations, and human hair follicles express functional receptors for TSH. Therefore, we asked whether the epidermis of normal human skin is yet another extrathyroidal target of TSH and whether epidermis even produces TSH. If so, we wanted to clarify whether intraepidermal TSH expression is regulated by TRH and/or thyroid hormones and whether TSH alters selected functions of normal human epidermis in situ.

Hair loss as a result of cutaneous autoimmunity: frontiers in the immunopathogenesis of primary cicatricial alopecia.

Primary cicatricial alopecias (PCA) represent uncommon inflammatory disorders that result in permanent loss of scalp hair. Cutaneous autoimmunity, most prominently chronic cutaneous lupus erythematosus (CCLE), can result in this kind of scarring hair loss. The cosmetic disfigurement caused by PCA and the very unsatisfactory therapeutic options available to date all demand a better understanding of the obscure pathobiology of PCA so as to define new therapeutic targets and strategies.

Immune privilege and the skin.

This chapter summarizes the evidence that defined compartments of the hair follicle (HF) and nail epithelium maintain an area of relative immune privilege (IP). HF and nail IP is chiefly characterized by absent or very low level of expression of major histocompatibility complex class Ia antigens, complemented by a number of factors, such as the local production of potent immunosuppressive agents, dysfunction of professional antigen-presenting cells and inhibition of natural killer cell activities. In the hair bulb, IP is seen only in the anagen stage of HF cycling, while the nail apparatus continuously maintains an IP site in its proximal nail matrix, since the nail apparatus does not cycle.