Mechanisms of tolerance and potential therapeutic interventions in Alopecia Areata

Abstract

This review aims to address the mechanisms of compromised immune tolerance contributing to the development and maintenance of Alopecia Areata (AA). Our goal is to also highlight future treatment opportunities and therapeutics that will safely and efficiently restore hair growth and maintain patients in remission. AA is a presumptive autoimmune disorder that coincides and genetically clusters to several other autoimmune diseases. In this review, we pay attention to the learnings from the mechanistic research and drug development in these other autoimmune conditions. Interestingly, most of these diseases have been linked to compromised central and peripheral tolerance, and increased intestinal inflammation with enhanced gut permeability. Break of tolerance and priming of the autoreactive T-cells to attack antigenic epitopes in the hair follicle most likely requires several steps which include escape from negative selection and compromised peripheral tolerance. Local skin-related changes are also of importance due to the patchy manifestation of the skin areas with loss of hair, particularly in the early disease. Here, we discuss the defective mechanisms of tolerance, both central and peripheral, and hypothesize that the disease is driven by areas of tolerance break, and that these could be targeted for successful therapeutic interventions.

Hair regrowth following fecal microbiota transplantation in an elderly patient with alopecia areata: A case report and review of the literature

“…However, the association between alopecia areata and gut dysbiosis awaits to be elucidated. Alopecia areata may link with other autoimmune diseases, especially with IBD[30]. A series of clinical cases reported that hair loss was found in patients with IBD[31-34], with little knowledge of its causes.…”

The gut microbiome alterations in allergic and inflammatory skin diseases – an update

“…The correlation of microbiome role in the autoimmune disease pathogenesis has been also contributed to microbial role immune mechanisms modulation . Several studies indicate that the loss of intestinal barrier integrity in local and systemic inflammation induction as well as autoimmunity . Literature data on the gastrointestinal role in AA indicate a higher prevalence of AA in patients with ulcerative colitis than in general population .…”

“…125 Several studies indicate that the loss of intestinal barrier integrity in local and systemic inflammation induction as well as autoimmunity. 126 Literature data on the gastrointestinal role in AA indicate a higher prevalence of AA in patients with ulcerative colitis than in general population. 127,128 Contradictory results were presented by Kim et al, 129 who observed no higher AA prevalence in the course of IBD.…”

Alopecia areata: a review of disease pathogenesis

“…So far none of the traditional immunosuppressants and newer targeted treatments have been able to establish long‐lasting remission. This is attributed to the heterogeneous nature of the immune responses in AA, which cannot be targeted with a single agent, and the lack of anagen induction in the resting (catagen and telogen) HFs following restoration of IP …”

“…This is attributed to the heterogeneous nature of the immune responses in AA, which cannot be targeted with a single agent, 193 and the lack of anagen induction in the resting (catagen and telogen) HFs following restoration of IP. 194 A number of suggestions have been made regarding future therapies, such as induction of peripheral tolerance in T cells, re-establishment of IP via administration of immune guardians, targeting the neuroendocrine-immune system and utilizing MIF ( Table 4, Fig. 4).…”