ArticleImmunity2026
UV irradiation drives lineage-specific MITF-mediated transcription of PD-L1 to confer immune tolerance to UV-mutated melanocytes.
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Article in Immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.
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36 authors.
Jennifer A LoCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Dermatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Inbal RachminCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Jessica L FlesherCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Xunwei WuCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Akinori KawakamiCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Dermatology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Miroslav HejnaDepartment of Physics, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Judith R BoozerCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Nhu NguyenCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Andrew D KingCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Yawen JiCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Stomatology, Central Hospital Affiliated to Shandong First Medical University, Jinan 250013, Shandong, China.
Sharon GermanaCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Lajos V KemenyCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; HCEMM-SU Translational Dermatology Research Group, Semmelweis University, Budapest 1085, Hungary; Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest 1094, Hungary; Department of Dermatology, Venereology and Dermatooncology, Faculty of Medicine, Semmelweis University, Budapest 1085, Hungary; MTA-SE Lendület "Momentum" Dermatology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest 1085, Hungary.
Anita A J van der SandeCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Jeffrey B ChengDepartment of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA; Dermatology Service, San Francisco Veterans Administration Health Care System, San Francisco, CA 94121, USA.
Michal LotemLautenberg Center for Immunology and Cancer Research, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel; Center for Melanoma and Cancer Immunotherapy, Sharett Institute of Oncology, Jerusalem 91120, Israel; Hadassah Cancer Research Institute, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel.
Torrey R UtneCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Yao ZhanCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Elisabeth M RoiderCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Dermatology, University Hospital of Basel, 4031 Basel, Switzerland.
Nisma MujahidCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Department of Dermatology, University of Utah, Salt Lake City, UT 84132, USA.
Elizabeth H ByrneCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Shailbala SinghDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Manoubia SaidaniIStem, CECS, Corbeil-Essonnes 91100, France.
Sabrina MartineauUniversité Paris-Saclay, Université d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France.
Nathalie HolicUniversité Paris-Saclay, Université d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France.
Christine BaldeschiUniversité Paris-Saclay, Université d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France.
Cécile MartinatUniversité Paris-Saclay, Université d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France.
Gordon J FreemanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Nir HacohenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02142, USA.
Keith T FlahertyMass General Brigham Cancer Institute, Boston, MA 02114, USA.
Genevieve M BolandDepartment of Surgery, Massachusetts General Hospital, Boston, MA 02114, USA; Krantz Family Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114, USA.
Jun S SongDepartment of Physics, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Arlene H SharpeDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Gene Lay Institute of Immunology and Inflammation of Brigham and Women's Hospital, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shadmehr DemehriCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Cassian YeeDepartment of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Parker Institute of Cancer Immunotherapy, San Francisco, CA 94129, USA.
Jennifer AlloucheCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Université Paris-Saclay, Université d'Evry, Inserm, IStem, UMR861, Corbeil-Essonnes 91100, France. Electronic address: jeallouche@gmail.com.
David E FisherCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA. Electronic address: dfisher3@mgh.harvard.edu.
Funding
Treating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI David McDermott · 2003 to 2026
$53.4MMedical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MTransgenic/KnockoutP01AI056299 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI SHARPE, ARLENE H. · 2003 to 2023
$42.5MTranscriptional mechanisms and melanomaP01CA163222 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DAVID E FISHER · 2013 to 2026
$25.3MThe MITF transcriptional network: melanoma risk and carcinogenesisR01AR043369 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DAVID E FISHER · 1996 to 2026
$9.4MPredicting Transcriptional and Epigenetic Networks in Cancer from Sequencing DataR01CA163336 · NCI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Jun S Song · 2012 to 2026
$4.4MTherapeutic strategies for treatment of giant congenital melanocytic neviR01AR072304 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DAVID E FISHER · 2017 to 2026
$3.9MRole of DNA Methylation and Hydroxymethylation in Epidermal HomeostasisK08AR067243 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHENG, JEFFREY B · 2015 to 2019
$834kCSRD VA I01 CX002608NCI NIH HHS P01 CA163222NCI NIH HHS P50 CA101942NCI NIH HHS R01 CA163336NIAID NIH HHS P01 AI056299NIAMS NIH HHS K08 AR067243NIAMS NIH HHS R01 AR043369NIAMS NIH HHS R01 AR072304NIGMS NIH HHS T32 GM007753
Abstract
UV radiation (UVR) drives high mutational burdens, yet precursor melanocytes accumulate these mutations without triggering immune clearance. Here, we investigated whether melanocyte-intrinsic transcriptional program(s) underlie immune tolerance to mutations resulting from UVR exposure. In primary human melanocytes, expression of PD-L1 (CD274) was dependent on microphthalmia-associated transcription factor (MITF), a crucial regulator of melanocyte development and an intermediate in the UV-tanning pathway. MITF directly activated PD-L1 transcription by binding a conserved upstream enhancer containing functional E-box elements. MITF determined both baseline melanocytic PD-L1 expression in healthy skin and its induction following UVR, independent of interferon signaling. Melanocyte-restricted Pd-l1 deletion in mice triggered CD8
Indexed as
B7-H1 AntigenImmune ToleranceMelanocytesMicrophthalmia-Associated Transcription FactorUltraviolet RaysAnimalsApoptosisCD8-Positive T-LymphocytesCell LineageCells, CulturedHumansMiceMutationTranscription, GeneticVitiligoB7-H1 AntigenCD274 protein, humanMicrophthalmia-Associated Transcription FactorMITF protein, humanautoimmunityimmune checkpointimmune privilegeimmune tolerancemelanocytesmicrophthalmia-associated transcription factorMITFPD-L1/CD274programmed death-ligand 1UV radiationvitiligo
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