The role of lymphocytes in the development and treatment of alopecia areata

Abstract

Alopecia areata (AA) development is associated with both innate and adaptive immune cell activation, migration to peri- and intra-follicular regions, and hair follicle disruption. Both CD4⁺ and CD8⁺ lymphocytes are abundant in AA lesions; however, CD8⁺ cytotoxic T lymphocytes are more likely to enter inside hair follicles, circumstantially suggesting that they have a significant role to play in AA development. Several rodent models recapitulate important features of the human autoimmune disease and demonstrate that CD8⁺ cytotoxic T lymphocytes are fundamentally required for AA induction and perpetuation. However, the initiating events, the self-antigens involved, and the molecular signaling pathways, all need further exploration. Studying CD8⁺ cytotoxic T lymphocytes and their fate decisions in AA development may reveal new and improved treatment approaches.

Keywords:

• alopecia areata
• autoimmune inflammation
• hair follicles
• lymphocytes
• pathogenesis
• treatment

Financial & competing interests disclosure

This work was supported by grants from the North American Hair Research Society (NAHRS) and the Canadian Dermatology Foundation (CDF). K McElwee is a recipient of the Canadian Institutes of Health Research (MSH-95328) and Michael Smith Foundation for Health Research [CI-SCH-00480(06-1)] investigator awards. K McElwee and J Shapiro are founders and shareholders of Replicel Life Sciences Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Alopecia areata (AA) is a hair follicle-specific autoimmune disease involving both innate and adaptive immune cells.

• Activated lymphocytes, along with antigen-presenting cells, synergize to initiate and promote AA.

• CD8+ cytotoxic T lymphocytes are fundamentally required for AA induction and perpetuation.

• The function of regulatory T cells may be defective in AA.

• Hair follicles normally exhibit immune privilege, but these properties may be deficient in AA.

• Blockade of antigen presentation and co-stimulation may prevent lymphocyte activation.

• Targeting immune cells and their cytokine production may be effective in AA treatment.

• Promoting regulatory T cells may restore immune system balance.

• Restoring or augmenting hair follicle immune privilege may prevent AA pathogenesis.

Notes