Understanding the significance of cytokines and chemokines in the pathogenesis of alopecia areata

Abstract

Alopecia areata has basically been understood as a type 1 inflammatory disease. Activated NKG2D+CD8+ cells produce the Th1 cytokine interferon‐γ, which leads to the disruption of immune tolerance of hair follicles and the exposure of self‐antigens. This results in dense inflammatory cell infiltration and apoptosis around hair follicles, inducing hair loss. A well‐known complication of alopecia areata is atopic dermatitis, a typical type 2 inflammatory disease. Hair scientists have shied away from confronting and understanding how alopecia areata, a type 1 inflammatory disease, and atopic dermatitis, a type 2 inflammatory disease, can occur together. This review summarizes the research on the cytokine balance in alopecia areata and then focuses on the classification of the cytokine balance in alopecia areata, including the classification of atopic dermatitis into extrinsic and intrinsic types. Dupilumab reportedly showed dual efficacy in a patient with concomitant atopic dermatitis and alopecia areata, supporting our own experience. Elevated Th2 cytokine levels have also been reported in patients with alopecia areata, with increased serum IL‐4, IL‐5, IL‐6 levels, high IgE levels and elevated eosinophil levels. Because local immunotherapy is a treatment that induces Th2‐type inflammation, it may worsen the condition of alopecia areata patients with extrinsic atopic dermatitis. It is desirable to select appropriate treatments with consideration of the cytokine balance.

IFN‐α and TNF‐α serum levels and their association with disease severity in Egyptian children and adults with alopecia areata

“…IFN-a is a type 1 IFN that is secreted in response to threat signals. 7 Until recently, IFN-c was considered the key cytokine in initiating AA, and the role of IFN-a was restricted to AA induction secondary to viral infection. 30,31 Three studies have revealed the essential role of IFN-a in starting AA, even in the absence of a preceding viral infection, via the enhancement of Th1 immune response surrounding hair bulbs, the stimulation of IFN-c production, the induction of the hair follicle immune privilege collapse, and the initiation of hair bulb apoptosis.…”

“…In addition to its antiviral activity, IFN-a has antitumor and immunomodulatory effects. [5][6][7] The role of IFN-a in noninfectious inflammatory diseases such as systemic lupus erythematosus, lichen planus, and psoriasis has been reported in several studies. [8][9][10] The role of IFN-a in AA has been suggested in reported cases of AA during IFN-a-2b and ribavirin therapy for hepatitis C virus infection.…”

Italian Survey for the Evaluation of the Effects of Coronavirus Disease 2019 (COVID-19) Pandemic on Alopecia Areata Recurrence

“…AA is a chronic autoimmune inflammatory disease characterized by sudden hair loss typically with a course of spontaneous remission and exacerbation [4,5]. The loss of immune privilege is reported as the main trigger of AA [6], but also inflammation and acute or chronic psycho-emotional stress have been reported as causative agents of AA as contributors to its progress [7,8]. Indeed, inflammatory skin diseases, including AA, can be exacerbated by psychological stress via stimulation of the neuroendocrine system [9].…”

Selective inhibition of JAK3 signaling is sufficient to reverse alopecia areata

“…However, the 4 JAK2-selective inhibitors in our study had little effect on AA disease reversal. We and others previously showed that IFN-γ plays a critical role in disease induction ( 31 ), whereas in chronic AA, numerous inflammatory cytokines (including IFN-γ) have been implicated in the disease ( 32 ). Additionally, we and others previously showed that both type I and type II IFN (IFN-γ) signaling pathways are active in the alopecia skin both from human patients with AA and C3H/HeJ mice with AA by gene microarray assays ( 33 ).…”