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IP is relative, not absolute, and is primarily based on absent, or greatly reduced, intra\u2010follicular antigen presentation via MHC class I and II molecules, along with prominent expression of \u201cno danger\u201d signals like CD200 and the creation of an immunoinhibitory signalling milieu generated by the secretory activities of HFs. Perifollicular mast cells, Tregs and other immunocytes may also contribute to HF IP maintenance in healthy human skin. Collapse of anagen hair bulb IP is an essential prerequisite for the development of alopecia areata (AA). In AA, lesional HFs are rapidly infiltrated by NKG2D\u00a0+\u00a0T cells and natural killer (NK) cells, while perifollicular mast cells acquire a profoundly pro\u2010inflammatory phenotype and interact with autoreactive CD8+ T cells. Using animal models, significant functional evidence has accumulated that demonstrates the dominance of the immune system in AA pathogenesis. Purified CD8+T\u2010cell\u00a0and NK cell populations alone, which secrete f\u03b3, suffice to induce the AA phenotype, while CD4+T\u2010cells aggravate it, and Tregs and iNKT cells may provide relative protection against AA development. While IP collapse may be induced by exogenous agents, inherent IP deficiencies might confer increased susceptibility to AA for some individuals. Thus, a key goal for effective AA management is the re\u2010establishment of a functional HF IP, which will also provide superior protection from disease relapse.<\/jats:p>","DOI":"10.1111\/exd.14155","type":"journal-article","created":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T17:36:30Z","timestamp":1595093790000},"page":"703-725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":301,"title":["Hair follicle immune privilege and its collapse in alopecia areata"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5927-6998","authenticated-orcid":false,"given":"Marta","family":"Bertolini","sequence":"first","affiliation":[{"name":"Monasterium Laboratory M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1020-3832","authenticated-orcid":false,"given":"Kevin","family":"McElwee","sequence":"additional","affiliation":[{"name":"Monasterium Laboratory M\u00fcnster Germany"},{"name":"Centre for Skin Sciences University of Bradford Bradford UK"},{"name":"Department of Dermatology and Skin Science University of British Columbia Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4267-2986","authenticated-orcid":false,"given":"Amos","family":"Gilhar","sequence":"additional","affiliation":[{"name":"Laboratory for Skin Research Rappaport Faculty of Medicine Technion\u2010Israel Institute of Technology Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5764-8516","authenticated-orcid":false,"given":"Silvia","family":"Bulfone\u2010Paus","sequence":"additional","affiliation":[{"name":"Monasterium Laboratory M\u00fcnster Germany"},{"name":"Centre for Dermatology Research University of Manchester and NIHR Manchester Biomedical Research Centre Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3492-9358","authenticated-orcid":false,"given":"Ralf","family":"Paus","sequence":"additional","affiliation":[{"name":"Monasterium Laboratory M\u00fcnster Germany"},{"name":"Centre for Dermatology Research University of Manchester and NIHR Manchester Biomedical Research Centre Manchester UK"},{"name":"Dr. Philip Frost Department of Dermatology &amp; Cutaneous Surgery University of Miami Miller School of Medicine Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2004.09.014"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4233"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2018.03.007"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1103442"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.11"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jisp.2017.10.014"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.c3671"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32987-8"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.04.002"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1679197"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-869-0_29"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198509000-00010"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2016.01.019"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gah129"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00435.x"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2006.00431.x"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0070-8"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.04.021"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940010900306"},{"key":"e_1_2_15_21_1","first-page":"58","volume":"29","author":"Medawar P. 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