Lymphocytes, neuropeptides, and genes involved in alopecia areata

Abstract

Many lessons in autoimmunity -particularly relating to the role of immune privilege and the interplay between genetics and neuroimmunology -can be learned from the study of alopecia areata, the most common cause of inflammation-induced hair loss. Alopecia areata is now understood to represent an organ-restricted, T cell-mediated autoimmune disease of hair follicles. Disease induction is associated with collapse of hair follicle immune privilege in both humans and in animal models. Here, the role of HLA associations, other immunogenetic factors, and neuroendocrine parameters in alopecia areata pathogenesis are reviewed. This instructive and clinically significant model disease deserves more widespread interest in the immunology community.Nonstandard abbreviations used: AA, alopecia areata; AIRE, autoimmune regulator; APECED, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy; IP-10, IFN-g-inducible protein 10; MIC, MHC class I chain-related; MIF, macrophage migration inhibitory factor; α-MSH, α-melanocyte-stimulating hormone; NALP1, NACHT leucine-rich-repeat protein 1; NGF, nerve growth factor.

Thyroid Autoimmunity in Patients with Skin Disorders

“…Alopecia areata offers many benefits as a model for the study of autoimmunity, in that it can be used to identify the contributing roles of immunogenetics and neuroendocrine factors in the initiation and propagation of autoimmune disease [24].…”

“…This disorder affects both sexes equally and occurs at all ages, although children and young adults are affected most often. The etiopathogenesis of AA is still unclear, but there is evidence that autoimmunity and endocrine dysfunction may be involved [24][25][26]. The autoimmune etiology has been proposed on the basis of its association with various autoimmune diseases, the presence of autoantibodies and various underlying immune abnormalities in the affected sites of these patients [27,28].…”

(Neuro-)endocrinology of epithelial hair follicle stem cells

“…In the past, almost all interest in the field has focused on thewell-recognized and long-studied, but still insufficiently characterized -impact of these hormones, neuropeptides, neurotransmitters and neurotrophins on the more differentiated progeny of HFeSC, namely on hair matrix keratinocytes and HF outer root sheath (ORS), on the melanocytes of the HF pigmentary unit, and on the specialized, inductive mesenchyme of the HF (connective tissue sheath and follicular dermal papilla) (Alonso and Fuchs, 2006;Gilhar et al, 2007;Slominski et al, 2005;Stenn and Paus, 2001). Now, however, there is growing awareness that HFeSCs themselves may underlie hormonal controls, and that the latter may well impact on hair normal follicle development, growth, cycling, hair shaft formation, and hair pigmentation.…”

“…It had long been thought that only the anagen hair bulb epithelium is a site of relative immune privilege, where e.g. immunogenic, melanogenesis-associated autoantigens are shielded from potentially deleterious autoimmune responses, and that the collapse of this anagen hair bulb immune privilege is a critical step in the pathogenesis of the most common autoimmune hair growth disorder, alopecia areata (Gilhar et al, 2007;Paus et al, 2005).…”

Limited Effectiveness of Platelet-Rich-Plasma Treatment on Chronic Severe Alopecia Areata

“…Patients with AA have been found to have an increased frequency of hair follicle-specific auto-antibodies [10]. The inferior portion of the normal hair follicle is an "immune privileged" site which is protected from surveillance by T cells [11]. Major Histocompatibility Complex (MHC) class I and II, molecules that bind and present pathogens to the immune system, are not expressed in normal hair follicle epithelium.…”