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Alopecia areata (AA) is an autoimmune hair loss disorder with no cure. Patients with sequence variation in AIRE are 15 times more likely to develop AA than the general population, yet the roles of AIRE in AA pathogenesis are unknown. In this study, we report that 62% of C57BL/6J female Aire ‒/‒ mice spontaneously developed persistent AA-like lesions that displayed several hallmarks of human AA. Lesional Aire ‒/‒ skin exhibited hair follicle (HF) dystrophy as determined by a reduced number of anagen HFs, decreased anagen HF proliferation, hair pigmentary changes, and decreased hair width and length. Inflammatory infiltrate comprising CD8 + T cells, CD4 + T cells, CD68 + macrophages, and mast cells was prominent in lesional Aire ‒/‒ HFs. From gene expression analyses, we found lesional Aire ‒/‒ skin to have significantly increased expression of human AA signature genes, including H2-Ab1, Ifnγ, IFN-γ‒induced chemokines (Ccl5, Cxcl9‒11), γ c family cytokine receptor Il2RA, and JAK‒signal transducer and activator of transcription (STAT) signaling components (Stat1, Stat2, Stat4). By immunostaining, lesional Aire ‒/‒ HFs also show upregulated major histocompatibility complex class I and downregulated α-melanocyte-stimulating hormone, signifying immune privilege collapse, and increased STAT1 activation in HF keratinocytes. Our study highlights a role for AIRE in HF biology and shows that Aire ‒/‒ mice may serve as a valuable model system to study AA pathogenesis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Unchecked inflammation, impaired keratinocyte differentiation, and heightened host defense responses typify psoriasis. Lambert et al. make clever use of psoriasis patient genetics and whole transcriptome RNA-Seq analysis to implicate Act1 in these seemingly variegated processes by keeping IL-17 receptor signaling in check while supporting differentiation and limiting innate immune responses in human keratinocytes., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Intermediate filaments are assembled from a diverse group of evolutionary conserved proteins and are specified in a tissue-dependent, cell type-dependent, and context-dependent fashion in the body. Genetic mutations in intermediate filament proteins account for a large number of diseases, ranging from skin fragility conditions to cardiomyopathies and premature aging. Keratins, the epithelial-specific intermediate filaments, are now recognized as multi-faceted effectors in their native context. In this review, we emphasize the recent progress made in defining the role of keratins towards the regulation of cytoarchitecture, cell growth and proliferation, apoptosis, and cell motility during embryonic development, in normal adult tissues, and in select diseases such as cancer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)