Oxidative stress and alopecia areata

Abstract

Alopecia areata (AA) is an inflammatory autoimmune disease characterized by non-scarring hair loss on the scalp or any other part of the hair-bearing skin. While the collapse of the immune privilege is considered as one of the most accepted theories accounting for AA, the exact pathogenesis of this disease remains unclear by now. Other factors, such as genetic predisposition, allergies, microbiota, and psychological stress, also play an important role in the occurrence and development of AA. Oxidative stress (OS), an unbalance between the oxidation and antioxidant defense systems, is believed to be associated with AA and may trigger the collapse of hair follicle-immune privilege. In this review, we examine the evidence of oxidative stress in AA patients, as well as the relationship between the pathogenesis of AA and OS. In the future, antioxidants may play a new role as a supplementary therapy for AA.

Keywords: alopecia areata; antioxidants; autoimmune; oxidative stress; reactive oxygen species.

Figure 1

The positive feedback-loop of losing hair follicle-immune privileges and its relationship with oxidative stress. In AA, stimulating factors such as UVB or natural light irradiation can induce the chemotaxis of various inflammatory cells around hair follicular epithelial cells (HFECs). HFECs upregulate the expression of MHC and NKG2D ligands, and then NKG2D + CD4 + T cells become effector T cells after binding to MHC I antigen complex and NKG2D ligands on its surface. Activated T cells produce IFN-γ via JAK1 and JAK3, and IFN-γ stimulates IL-15 production in HF-ecs via JAK1 and JAK2. Then, IL-15 again binds to CD8 + NKG2D + T cells to produce more IFN-γ, forming a positive feedback loop that leads to the collapse of immune privilege of hair follicles and promotes the autoimmune attack of hair follicles by inflammatory cells, such as dendritic cells, CD4 + T cells, NK T cells, and mast cells. IFN-γ and IL-1β are oxidative stress triggers, and IFN-γ is a key player in XO-mediated oxidative stress. Light irradiation can induce an increase in XO enzyme activity, producing more oxygen free radicals. In addition, skin inflammation caused by UV irradiation synthesized large amounts of ·NO in the presence of the iNOS enzyme. IFN-γ and IL-1β can induce the rapid expression of iNOS and lead to O₂^•− produced by XO forming ONOO−, which then decompose into ·NO2 and ·OH, causing free radical reactions, including lipid free radicals (MDA, etc.), protein free radicals and DNA free radicals (8-OHdG, etc.). These ROS can promote the upregulation of NKG2D ligands such as ULBP, which triggers the loss of immune immunity of hair follicles and promotes the development of AA. INFγ, interferon gamma; STAT, signal transducer and activator; P, phosphorylated; TCR, T cell receptor; NKG2D, NK cell receptor D; XO, xanthine oxidase; and iNOS, inducible nitric oxide synthase.