Alopecia areata (AA) is a non-scarring hair loss disorder caused by autoimmunity. The immune collapse of the hair follicle, where interferon-gamma (IFN-γ) and CD8+ T cells accumulate, is a key factor in AA. However, the exact functional mechanism remains unclear. Therefore, AA treatment has poor efficacy maintenance and high relapse rate after drug withdrawal. Recent studies show that immune-related cells and molecules affect AA. These cells communicate through autocrine and paracrine signals. Various cytokines, chemokines and growth factors mediate this crosstalk. In addition, adipose-derived stem cells (ADSCs), gut microbiota, hair follicle melanocytes, non-coding RNAs and specific regulatory factors have crucial roles in intercellular communication without a clear cause, suggesting potential new targets for AA therapy. This review discusses the latest research on the possible pathogenesis and therapeutic targets of AA.

Cytotoxic T lymphocyte has been a concern for the etiopathogenesis of alopecia areata (AA), some recent evidence suggests that the regulatory T (Treg) cell deficiency is also a contributing factor. In the lesional scalp of AA, Treg cells residing in the follicles are impaired, leading to dysregulated local immunity and hair follicle (HF) regeneration disorders. New strategies are emerging to modulate Treg cells’ number and function for autoimmune diseases. There is much interest to boost Treg cells in AA patients to suppress the abnormal autoimmunity of HF and stimulate hair regeneration. With few satisfactory therapeutic regimens available for AA, Treg cell-based therapies could be the way forward. Specifically, CAR-Treg cells and novel formulations of low-dose IL-2 are the alternatives.