{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T19:10:58Z","timestamp":1790104258796,"version":"4.0.1"},"reference-count":147,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Autoimmune and immune-mediated alopecias demonstrate how a site-specific failure of immune privilege can produce reversible or irreversible hair loss. In alopecia areata (AA), cytotoxic injury is concentrated at the anagen bulb but preserves the stem cell pool, permitting regrowth following immune suppression. Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) feature a spectrum of chronic interface dermatitis that destroys the stem cell niche, leading to permanent fibrosis. These entities overlap in bulge-targeted inflammation and histopathology but diverge in clinical distribution and demographic risk. Discoid lupus erythematosus (DLE) of the scalp reflects immune-complex\u2013driven complement injury to the upper follicle, whereas central centrifugal cicatricial alopecia (CCCA) represents a fibroblast-dominant process associated with chronic stress and is sustained by stromal remodeling. Here, we frame these entities as four follicular immune network archetypes defined by the axial locus of immune privilege collapse, effector programs, loss of tolerogenic programs, stromal trajectories, and dermoscopic correlates. Using a Network Engineering for Site-Specific Tolerance (NEST) framework, we situate these archetypes within a three-tier taxonomy comprising intrinsic follicular privilege, local tolerogenic repertoires, and stromal checkpoint circuits. Specifically, AA localizes to the anagen bulb, DLE spans the upper follicle and interfollicular epidermis, LPP\/FFA targets the bulge stem cell niche, and CCCA converges on the upper follicle\u2013interfollicular epidermis unit. Within their respective niches, AA and DLE exhibit comparatively resolved clonotypic effector modules dominated by pathogenic T cells or B cells, whereas LPP\/FFA and CCCA are framed as polyclonal networks in which the failure of tolerogenic programs or stress signaling pathways constitutes the dominant archetypal engine.<\/jats:p>","DOI":"10.3389\/fmed.2026.1805170","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:32:52Z","timestamp":1774935172000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Hair follicle immune privilege in autoimmune and immune-mediated alopecias: paths toward reestablishing immune tolerance"],"prefix":"10.3389","volume":"13","author":[{"given":"Pedram","family":"Shafiei-Jahani","sequence":"first","affiliation":[{"name":"David Geffen School of Medicine at the University of California, Los Angeles","place":["Los Angeles, CA, United States"]},{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitis","family":"Akbari","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Haniff","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine at the University of California, Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Ziprick","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine at the University of California, Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Carlisle","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine at the University of California, Los Angeles","place":["Los Angeles, CA, United States"]},{"name":"Division of Dermatology, Department of Medicine, University of California, Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Goh","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine at the University of California, Los Angeles","place":["Los Angeles, CA, United States"]},{"name":"Division of Dermatology, Department of Medicine, University of California, Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Holland","sequence":"additional","affiliation":[{"name":"David Geffen School of Medicine at the University of California, Los Angeles","place":["Los Angeles, CA, United States"]},{"name":"Division of Dermatology, Department of Medicine, University of California, Los Angeles","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omid","family":"Akbari","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California","place":["Los Angeles, CA, United 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