{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T03:38:59Z","timestamp":1784432339054,"version":"3.55.0"},"reference-count":77,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T00:00:00Z","timestamp":1718064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100007155","name":"Medical Research Council Clinical Research Fellowship to D.R.","doi-asserted-by":"publisher","award":["MR\/N025989\/1"],"award-info":[{"award-number":["MR\/N025989\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Roche\/Genentech"},{"name":"National Institute for Health and Care Research Manchester Biomedical Research Centre"},{"name":"Forst Endowed Scholarship"},{"name":"Department of Dermatology, University of Miami"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Inhibitors of epidermal growth factor receptor (EGFRi) or mitogen-activated kinase (MEKi) induce a folliculitis in 75\u201390% of patients, the pathobiology of which remains insufficiently understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To characterize changes in the skin immune status and global transcriptional profile of patients treated with EGFRi; to investigate whether EGFRi affects the hair follicle\u2019s (HF) immune privilege (IP); and to identify early proinflammatory signals induced by EGFRi\/MEKi in human scalp HFs ex vivo.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Scalp biopsies were taken from patients exhibiting folliculitis treated long term with EGFRi (\u2018chronic EGFRi\u2019 group, n = 9) vs. healthy scalp skin (n = 9) and patients prior to commencing EGFRi treatment and after 2 weeks of EGFRi therapy (\u2018acute EGFRi\u2019 group, n = 5). Healthy organ-cultured scalp HFs were exposed to an EGFRi (erlotinib, n = 5) or a MEKi (cobimetinib, n = 5). Samples were assessed by quantitative immunohistomorphometry, RNA sequencing (RNAseq) and in situ hybridization.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The \u2018chronic EGFRi\u2019 group showed CD8+ T-cell infiltration of the bulge alongside a partial collapse of the HF\u2019s IP, evidenced by upregulated major histocompatibility complex (MHC) class I, \u03b22-microglobulin (B2 M) and MHC class II, and decreased transforming growth factor-\u03b21 protein expression. Healthy HFs treated with EGFRi\/MEKi ex vivo also showed partial HF IP collapse and increased transcription of human leucocyte antigen (HLA)-A, HLA-DR and B2 M transcripts. RNAseq analysis showed increased transcription of chemokines (CXCL1, CXCL13, CCL18, CCL3, CCL7) and interleukin (IL)-26 in biopsies from the \u2018chronic EGFRi\u2019 cohort, as well as increased IL-33 and decreased IL-37 expression in HF biopsies from the \u2018acute EGFRi\u2019 group and in organ-cultured HFs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The data show that EGFRi\/MEKi compromise the physiological IP of human scalp HFs and suggest that future clinical management of EGFRi\/MEKi-induced folliculitis requires HF IP protection and inhibition of IL-33.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljae243","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T23:18:48Z","timestamp":1717802328000},"page":"791-804","source":"Crossref","is-referenced-by-count":10,"title":["Epidermal growth factor receptor\/mitogen-activated kinase inhibitor treatment induces a distinct inflammatory hair follicle response that includes collapse of immune privilege"],"prefix":"10.1093","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2860-1636","authenticated-orcid":false,"given":"David","family":"Rutkowski","sequence":"first","affiliation":[{"name":"Dermatology Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust , Manchester ,","place":["UK"]},{"name":"Manchester University Foundation Trust , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Scholey","sequence":"additional","affiliation":[{"name":"Manchester University Foundation Trust , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9482-1066","authenticated-orcid":false,"given":"John","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Safety Assessment, Genentech, Inc. , South San Francisco, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Pye","sequence":"additional","affiliation":[{"name":"Dermatology Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Blackhall","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust , Withington ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-6481","authenticated-orcid":false,"given":"Richard\u00a0B","family":"Warren","sequence":"additional","affiliation":[{"name":"Dermatology Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust , Manchester ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Mediteknia Skin and Hair Lab , Las Palmas de Gran Canaria ,","place":["Spain"]},{"name":"Universidad Fernando Pessoa Canarias , Las Palmas de Gran Canaria ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-4427","authenticated-orcid":false,"given":"Christopher E M","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Dermatology Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust , Manchester ,","place":["UK"]},{"name":"Department of Dermatology, King\u2019s College Hospital, King\u2019s College London , London 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