{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:32:20Z","timestamp":1793831540637,"version":"4.6.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"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. Immunol."],"abstract":"<jats:p>Halo nevus has historically been observed as a localized skin phenomenon surrounding a melanocytic nevus. However, emerging studies indicate that halo nevus serves as a model for immune-mediated, primarily CD8+ T cells\u2013targeted destruction of melanocytes, similar to vitiligo or regressing melanoma. The aim of this mini-review is to summarize the current understanding of the immunological mechanisms underlying halo nevus formation, to highlight similarities and differences between halo nevus and vitiligo, as well as contrasts with regressing melanoma. Acknowledging halo nevus as a model for a controlled immune response against melanocytes could offer valuable insights into understanding triggers, potential antigens, and the balance of effector and regulatory responses, with translational relevance to pigment disorders and tumor immunology.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1729726","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:48:17Z","timestamp":1770187697000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Immunological aspects of halo nevus (Sutton\u2019s Nevus)"],"prefix":"10.3389","volume":"17","author":[{"given":"Nika","family":"Hla\u010da","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijana","family":"Vi\u010di\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Prpi\u0107-Massari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.12843","article-title":"Halo nevus: review of the literature and clinicopathologic findings","volume":"54","author":"Weyant","year":"2015","journal-title":"Int J Dermatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"904","DOI":"10.3390\/jpm11090904","article-title":"Current challenges in deciphering Sutton nevi\u2014literature review and personal experience","volume":"11","author":"Nedelcu","year":"2021","journal-title":"J Pers Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2012.04504.x","article-title":"Association of halo nevus and vitiligo in childhood: a retrospective observational study","volume":"27","author":"Patrizi","year":"2013","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2011.04160.x","article-title":"Halo naevi with associated vitiligo-like depigmentations: pathogenetic hypothesis","volume":"26","author":"van Geel","year":"2012","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2017.03.008","article-title":"A similar local immune and oxidative stress phenotype in vitiligo and halo nevus","volume":"87","author":"Yang","year":"2017","journal-title":"J Dermatol Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1111\/pcmr.13037","article-title":"The delicate relation between melanocytes and skin immunity: A game of hide and seek","volume":"35","author":"Speeckaert","year":"2022","journal-title":"Pigment Cell Melanoma Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(97)70181-6","article-title":"The immune response in halo nevi","volume":"37","author":"Zeff","year":"1997","journal-title":"J Am Acad Dermatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2010.10154.x","article-title":"Prognostic value and clinical significance of halo naevi regarding vitiligo","volume":"164","author":"van Geel","year":"2011","journal-title":"Br J Dermatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2230.1998.00327.x","article-title":"Familial halo naevi","volume":"23","author":"Herd","year":"1998","journal-title":"Clin Exp Dermatol"},{"key":"B10","article-title":"Morphological features of melanocytic tumors with depigmented halo: review of the literature and personal results","volume":"56","author":"Nedelcu","year":"2015","journal-title":"Rom J Morphol Embryol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000000205","article-title":"Study of the immunophenotype of the inflammatory cells in melanomas with regression and halo nevi","volume":"37","author":"Botella-Estrada","year":"2015","journal-title":"Am J Dermatopathol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.25259\/IJDVL_505_20","article-title":"Halo phenomenon is not restricted to melanocytic lesions","volume":"88","author":"Vural","year":"2022","journal-title":"Indian J Dermatol Venereol Leprol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.002","article-title":"DAMPs and DAMP-sensing receptors in inflammation and diseases","volume":"57","author":"Ma","year":"2024","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-3083.2010.03790.x","article-title":"Halo phenomenon in melanocytic nevi (Sutton\u2019s nevi): does the diameter matter","volume":"25","author":"Rongioletti","year":"2011","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.5114\/pdia.2014.40963","article-title":"Dermoscopy of halo nevus in own observation","volume":"31","author":"Kami\u0144ska-Winciorek","year":"2014","journal-title":"Postepy Dermatol Alergol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2015.09.027","article-title":"Halo and pseudo-halo melanoma","volume":"74","author":"Suzuki","year":"2016","journal-title":"J Am Acad Dermatol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/pde.12041","article-title":"Dermoscopy for the pediatric dermatologist. Part III: dermoscopy of melanocytic lesions","volume":"30","author":"Haliasos","year":"2013","journal-title":"Pediatr Dermatol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.3.1789","article-title":"Immune-mediated destruction of melanocytes in halo nevi is associated with the local expansion of a limited number of T cell clones","volume":"162","author":"Musette","year":"1999","journal-title":"J Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"89","DOI":"10.3121\/cmr.2.2.89","article-title":"The immunopathology of regression in benign lichenoid keratosis, keratoacanthoma, and halo nevus","volume":"2","author":"Bayer-Garner","year":"2004","journal-title":"Clin Med Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.1994.tb00704.x","article-title":"Characterization of the mononuclear infiltrate involved in regression of halo nevi","volume":"21","author":"Akasu","year":"1994","journal-title":"J Cutan Pathol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"16580","DOI":"10.1038\/s41598-024-67494-9","article-title":"Analysis of granulysin expression in vitiligo and halo nevus","volume":"14","author":"Hla\u010da","year":"2024","journal-title":"Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","first-page":"110300","DOI":"10.1016\/j.clim.2024.110300","article-title":"Abnormal metabolism in melanocytes participates in the activation of dendritic cells in halo nevus","volume":"265","author":"Jiang","year":"2024","journal-title":"Clin Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S321672","article-title":"Transcriptome analysis reveals the molecular immunological characteristics of lesions in patients with halo nevi","volume":"14","author":"Pan","year":"2021","journal-title":"J Inflammation Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1124\/mol.115.098756","article-title":"UDP-Sugars as Extracellular Signaling Molecules: Cellular and Physiologic Consequences of P2Y14 Receptor Activation","volume":"88","author":"Lazarowski","year":"2015","journal-title":"Mol Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.105","article-title":"Neutrophil extracellular traps in immunity and disease","volume":"18","author":"Papayannopoulos","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1628913","article-title":"PD-L1+ neutrophils mediate immune regulation of CD8+ T cells in halo nevi","volume":"16","author":"Zhang","year":"2025","journal-title":"Front Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/ni1582","article-title":"Functions of natural killer cells","volume":"9","author":"Vivier","year":"2008","journal-title":"Nat Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-273953","article-title":"Granulysin activates antigen-presenting cells through TLR4 and acts as an immune alarmin","volume":"116","author":"Tewary","year":"2010","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1159\/000342757","article-title":"Foxp3+ regulatory T cells are increased in the early stages of halo nevi: clinicopathological features of 30 halo nevi","volume":"225","author":"Park","year":"2012","journal-title":"Dermatology"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2023.03.004","article-title":"Differences in the immune microenvironment between improved and non-improved cases of vitiligo after halo nevus excision","volume":"109","author":"Kano","year":"2023","journal-title":"J Dermatol Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.04.031","article-title":"Interferon receptor signaling pathways regulate PD-L1 and PD-L2 expression","volume":"19","author":"Garc\u00eda-D\u00edaz","year":"2017","journal-title":"Cell Rep"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.108","article-title":"The diverse functions of the PD-1 inhibitory pathway","volume":"18","author":"Sharpe","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/pde.12717","article-title":"Comparison of childhood vitiligo presenting with or without associated halo nevi","volume":"33","author":"Cohen","year":"2015","journal-title":"Pediatr Dermatol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4103\/0366-6999.218011","article-title":"Factors associated with development of vitiligo in patients with halo nevus","volume":"130","author":"Zhou","year":"2017","journal-title":"Chin Med J (Engl)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1111\/1346-8138.15743","article-title":"Vitiligo and autoimmunity: advances in pathogenesis and therapeutic perspectives","volume":"16","author":"Ezzedine","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2020.5032","article-title":"Association of histologic regression with a favorable outcome in patients with stage I and II cutaneous melanoma","volume":"157","author":"El Sharouni","year":"2021","journal-title":"JAMA Dermatol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02105","article-title":"Tumor-infiltrating lymphocytes and their prognostic value in cutaneous melanoma","volume":"11","author":"Maibach","year":"2020","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ad.2025.01.011","article-title":"Inflammatory cell immunophenotypes in regressing melanomas and halo nevi: possible keys to distinguish intensely inflamed tumors","volume":"116","author":"Brugu\u00e9s","year":"2025","journal-title":"Actas Dermosifiliogr"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1729726\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:48:18Z","timestamp":1770187698000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1729726\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":38,"alternative-id":["10.3389\/fimmu.2026.1729726"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1729726","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]},"article-number":"1729726"}}