Pathogenesis of Alopecia Areata and Vitiligo: Commonalities and Differences

• Published in: International journal of molecular sciences Vol. 25; no. 8; p. 4409
• Main Authors: Yamaguchi, Hiroki L., Yamaguchi, Yuji, Peeva, Elena
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024
• Subjects: Alopecia; Alopecia Areata - etiology; Alopecia Areata - immunology; Alopecia Areata - metabolism; Alopecia Areata - pathology; Animals; Antigens; Autophagy; B cells; Baldness; Biological response modifiers; Biomarkers; Celiac disease; Chemokines; Cytokines; Cytokines - metabolism; Cytomegalovirus; Cytotoxicity; Dendritic cells; Dermatitis; Hair loss; Humans; Immune Privilege; Interferon; Interleukins; Intermedin; Keratin; Ligands; Lymphocytes; Monoclonal antibodies; Pathogenesis; Pharmaceutical industry; Psoriasis; Skin; T cells; Thyroid diseases; Transforming growth factors; Viral infections; Vitiligo; Vitiligo - etiology; Vitiligo - immunology; Vitiligo - metabolism; Vitiligo - pathology; United States; natural killer cell receptor (NKG2D); hair bulge; keratinocyte; melanocyte; interleukin 15 receptor β (IL-15Rβ); MHC class 1 polypeptide-related sequence A (MICA); genome-wide association studies (GWAS); danger-associated molecular pattern (DAMP); indoleamine 2,3-dioxygenase (IDO); hair germ
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25084409

Both alopecia areata (AA) and vitiligo are distinct, heterogenous, and complex disease entities, characterized by nonscarring scalp terminal hair loss and skin pigment loss, respectively. In AA, inflammatory cell infiltrates are in the deep reticular dermis close to the hair bulb (swarm of bees), whereas in vitiligo the inflammatory infiltrates are in the epidermis and papillary dermis. Immune privilege collapse has been extensively investigated in AA pathogenesis, including the suppression of immunomodulatory factors (e.g., transforming growth factor-β (TGF-β), programmed death-ligand 1 (PDL1), interleukin-10 (IL-10), α-melanocyte-stimulating hormone (α-MSH), and macrophage migration inhibitory factor (MIF)) and enhanced expression of the major histocompatibility complex (MHC) throughout hair follicles. However, immune privilege collapse in vitiligo remains less explored. Both AA and vitiligo are autoimmune diseases that share commonalities in pathogenesis, including the involvement of plasmacytoid dendritic cells (and interferon-α (IFN- α) signaling pathways) and cytotoxic CD8+ T lymphocytes (and activated IFN-γ signaling pathways). Blood chemokine C-X-C motif ligand 9 (CXCL9) and CXCL10 are elevated in both diseases. Common factors that contribute to AA and vitiligo include oxidative stress, autophagy, type 2 cytokines, and the Wnt/β-catenin pathway (e.g., dickkopf 1 (DKK1)). Here, we summarize the commonalities and differences between AA and vitiligo, focusing on their pathogenesis.