In a recent study, researchers reviewed the immune mechanisms underlying alopecia areata (AA), focusing on how loss of hair follicle immune privilege drives disease and how recent findings are shaping new therapeutic targets. AA stems from breakdown of the hair follicle’s normal “immune privilege,” especially in the proximal follicle/bulge where immune surveillance is usually low. That protected state is maintained by reduced major histocompatibility complex (MHC) expression, dampened antigen presentation, and local immunosuppressive/inhibitory signals (e.g., POMC, TGF-β, MIF, CD200, VIPR). When immune privilege collapses—likely influenced by stress, epigenetic change, and genetic risk—MHC class I/II increases, immune cells infiltrate, and the autoimmune attack disrupts the hair cycle (shorter anagen, early catagen, prolonged telogen), causing hair loss.
Pathogenesis is driven mainly by NKG2D+ CD8+ T cells, amplified by an IFN-γ ↔ IL-15 positive feedback loop through JAK signaling and potentially sustained by clonally expanded and tissue-resident memory T cells. Other players may contribute (Th17, altered Tregs, γδ T cells, dendritic cells, mast cells, ILC1), supporting a multi-cell immune network model. Clinically, JAK inhibitors have the strongest evidence and include FDA-approved options, but relapse after stopping therapy is common. This is driving interest in approaches such as IL-2-based Treg support, cytokine/receptor blockade, S1P trafficking inhibitors, and dupilumab in Th2/atopic subsets. Additional emerging strategies include MSC-based therapies and newer molecular targets (SIRT1, RIPK1, OX40/OX40L, IKZF1, PPARα) aimed at more durable control.
Reference: Kim SY, Lee HJ, Heo J, Kim BJ, Seok J. Alopecia areata: from immunopathogenesis to emerging therapeutic approaches. Front Immunol. 2025 Nov 7;16:1681163. doi: 10.3389/fimmu.2025.1681163. PMID: 41280915; PMCID: PMC12634633.
Link: Alopecia areata: from immunopathogenesis to emerging therapeutic approaches – PMC
