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.

Figure 1. AA clinical presentation, histology, and immunohistochemistry.

(A) AA and (B) AA totalis. (C–F) Histology of AA: features include perifollicular and intrafollicular infiltrate of lymphocytes as well as dystrophy of the hair follicle (C). Immunochemistry demonstrating follicular expression of HLA-A,B,C (Dako) (D), HLA-DR (Biodesign) (E), and CD54 (also known as ICAM-1; Biodesign) (F). Original magnification, ×80 (C–E); ×160 (F).

Figure 2. A model of immune privilege collapse in AA pathogenesis.

Both a normal anagen (growing) hair follicle (A) and a hair follicle in AA (B) are shown. MHC class I molecules are expressed on the epidermis, and on the most superficial (distal) portion of the normal hair follicle epithelium. The inferior (proximal) portions of the hair follicle are immune privileged and deficient in expression of MHC classes I and II as well as APCs. By contrast, the AA anagen hair follicle expresses MHC class I and II molecules throughout the follicular epithelium, including the portion adjacent to the dermal papilla of the hair follicle. Active AA also exhibits a perifollicular infiltrate of CD4⁺ T cells and an intrafollicular infiltrate of CD8⁺ T cells. IRS, inner root sheath; ORS, outer root sheath.

Figure 3. Proposed pathogenesis of AA.

Cytokines and cellular factors responsible for maintaining immune privilege are listed in the left box. Those factors believed to mediate loss of immune privilege and initiation of disease are listed in the middle box. Loss of immune privilege is associated with expression of MHC class I molecules, which are capable of presenting hair follicle autoantigens to T lymphocytes. Secondary autoimmune amplification circuits that may help establish or amplify the pathology are listed in the right box.