A direct link between MITF, innate immunity, and hair graying

Melanocyte stem cells (McSCs) and mouse models of hair graying serve as useful systems to uncover mechanisms involved in stem cell self-renewal and the maintenance of regenerating tissues. Interested in assessing genetic variants that influence McSC maintenance, we found previously that heterozygosity for the melanogenesis associated transcription factor, Mitf, exacerbates McSC differentiation and hair graying in mice that are predisposed for this phenotype. Based on transcriptome and molecular analyses of Mitfmi-vga9/+ mice, we report a novel role for MITF in the regulation of systemic innate immune gene expression. We also demonstrate that the viral mimic poly(I:C) is sufficient to expose genetic susceptibility to hair graying. These observations point to a critical suppressor of innate immunity, the consequences of innate immune dysregulation on pigmentation, both of which may have implications in the autoimmune, depigmenting disease, vitiligo.

[1]  K. Ezzedine,et al.  New discoveries in the pathogenesis and classification of vitiligo. , 2017, Journal of the American Academy of Dermatology.

[2]  Stephanie A. Santorico,et al.  Multiple Functional Variants of IFIH1, a Gene Involved in Triggering Innate Immune Responses, Protect against Vitiligo. , 2017, The Journal of investigative dermatology.

[3]  Piul S. Rabbani,et al.  EdnrB Governs Regenerative Response of Melanocyte Stem Cells by Crosstalk with Wnt Signaling. , 2016, Cell reports.

[4]  D. Balding,et al.  A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features , 2016, Nature Communications.

[5]  Y. Okuno,et al.  PU.1-Induced IRF4 Down-Regulation and Subsequent IRF7 up-Regulation in Myeloma Cells , 2015 .

[6]  A. McCallion,et al.  Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes. , 2015, Human molecular genetics.

[7]  L. Larue,et al.  Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells , 2015, PLoS genetics.

[8]  S. Aerts,et al.  Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells , 2015, eLife.

[9]  K. Essien,et al.  Animal models of vitiligo: Matching the model to the question * , 2014 .

[10]  H. Yokozeki,et al.  Coupling of the radiosensitivity of melanocyte stem cells to their dormancy during the hair cycle , 2014, Pigment cell & melanoma research.

[11]  Ashley M. Zehnder,et al.  Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition , 2014, Genome research.

[12]  L. Lagae,et al.  Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling , 2014, Nature Genetics.

[13]  Oliver S. Burren,et al.  A Type I Interferon Transcriptional Signature Precedes Autoimmunity in Children Genetically at Risk for Type 1 Diabetes , 2014, Diabetes.

[14]  J. Richmond,et al.  Innate immune mechanisms in vitiligo: danger from within. , 2013, Current opinion in immunology.

[15]  Theresa Guo,et al.  A Polymorphism in IRF4 Affects Human Pigmentation through a Tyrosinase-Dependent MITF/TFAP2A Pathway , 2013, Cell.

[16]  W. Pavan,et al.  A Dual Role for SOX10 in the Maintenance of the Postnatal Melanocyte Lineage and the Differentiation of Melanocyte Stem Cell Progenitors , 2013, PLoS genetics.

[17]  S. Abraham,et al.  Innate Immunity and Its Regulation by Mast Cells , 2013, The Journal of Immunology.

[18]  M. Nishimura,et al.  Mutant HSP70 Reverses Autoimmune Depigmentation in Vitiligo , 2013, Science Translational Medicine.

[19]  A. Xu,et al.  Transcriptome Analysis Reveals Markers of Aberrantly Activated Innate Immunity in Vitiligo Lesional and Non-Lesional Skin , 2012, PloS one.

[20]  Simon Yu,et al.  INTERFEROME v2.0: an updated database of annotated interferon-regulated genes , 2012, Nucleic Acids Res..

[21]  L. Larue,et al.  B-Raf and C-Raf are required for melanocyte stem cell self-maintenance. , 2012, Cell reports.

[22]  Paul Shinn,et al.  Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. , 2012, Cancer cell.

[23]  S. Forster Interferon signatures in immune disorders and disease , 2012, Immunology and cell biology.

[24]  Jo Lambert,et al.  Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo , 2012, Nature Genetics.

[25]  J. Song,et al.  Understanding mechanisms of vitiligo development in Smyth line of chickens by transcriptomic microarray analysis of evolving autoimmune lesions , 2012, BMC Immunology.

[26]  S. Crampton,et al.  Ifih1 Gene Dose Effect Reveals MDA5-Mediated Chronic Type I IFN Gene Signature, Viral Resistance, and Accelerated Autoimmunity , 2012, The Journal of Immunology.

[27]  G. Barsh,et al.  Digital gene expression for non-model organisms. , 2011, Genome research.

[28]  M. Jolly,et al.  Autoimmune Disease Risk Variant of IFIH1 Is Associated with Increased Sensitivity to IFN-α and Serologic Autoimmunity in Lupus Patients , 2011, The Journal of Immunology.

[29]  Piul S. Rabbani,et al.  Coordinated Activation of Wnt in Epithelial and Melanocyte Stem Cells Initiates Pigmented Hair Regeneration , 2011, Cell.

[30]  H. Nakauchi,et al.  Hair follicle stem cells provide a functional niche for melanocyte stem cells. , 2011, Cell stem cell.

[31]  Sean Davis,et al.  Interferon-γ links ultraviolet radiation to melanomagenesis in mice. , 2011, Nature.

[32]  J. Borovanský,et al.  “Transcription physiology” of pigment formation in melanocytes: central role of MITF , 2010, Experimental dermatology.

[33]  F. Sanai,et al.  Interferon‐induced vitiligo in hepatitis C patients: a case series , 2010, International journal of dermatology.

[34]  Cory Y. McLean,et al.  GREAT improves functional interpretation of cis-regulatory regions , 2010, Nature Biotechnology.

[35]  Sheri L. Riccardi,et al.  Fine-mapping of vitiligo susceptibility loci on chromosomes 7 and 9 and interactions with NLRP1 (NALP1). , 2010, The Journal of investigative dermatology.

[36]  J. Roes,et al.  Key roles for transforming growth factor beta in melanocyte stem cell maintenance. , 2010, Cell stem cell.

[37]  C. Bertolotto,et al.  Fifteen‐year quest for microphthalmia‐associated transcription factor target genes , 2010, Pigment cell & melanoma research.

[38]  L. Larue,et al.  Transgenic expression of Notch in melanocytes demonstrates RBP‐Jκ‐dependent signaling , 2010, Pigment cell & melanoma research.

[39]  N. Binh,et al.  Genotoxic Stress Abrogates Renewal of Melanocyte Stem Cells by Triggering Their Differentiation , 2009, Cell.

[40]  C. Erickson,et al.  FOXD3 regulates the lineage switch between neural crest-derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism , 2009, Development.

[41]  R. Sékaly,et al.  Poly (I:C) induced immune response in lymphoid tissues involves three sequential waves of type I IFN expression. , 2009, Virology.

[42]  Osamu Takeuchi,et al.  Innate immunity to virus infection , 2009, Immunological reviews.

[43]  R. Dummer,et al.  Novel MITF targets identified using a two‐step DNA microarray strategy , 2008, Pigment cell & melanoma research.

[44]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[45]  L. Larue,et al.  Melanoblasts' proper location and timed differentiation depend on Notch/RBP-J signaling in postnatal hair follicles. , 2008, The Journal of investigative dermatology.

[46]  Shizuo Akira,et al.  Toll‐like Receptor and RIG‐1‐like Receptor Signaling , 2008, Annals of the New York Academy of Sciences.

[47]  T. Hornyak,et al.  Neurofibromin as a regulator of melanocyte development and differentiation , 2008, Journal of Cell Science.

[48]  B. Williams,et al.  The response of mammalian cells to double-stranded RNA. , 2007, Cytokine & growth factor reviews.

[49]  S. Locarnini,et al.  Toll‐like receptors, RIG‐I‐like RNA helicases and the antiviral innate immune response , 2007, Immunology and cell biology.

[50]  Sheri L. Riccardi,et al.  NALP1 in vitiligo-associated multiple autoimmune disease. , 2007, The New England journal of medicine.

[51]  Jane Goodall,et al.  Mitf regulation of Dia1 controls melanoma proliferation and invasiveness. , 2006, Genes & development.

[52]  D. Fisher,et al.  MITF: master regulator of melanocyte development and melanoma oncogene. , 2006, Trends in molecular medicine.

[53]  Richard A Flavell,et al.  Essential role of mda-5 in type I IFN responses to polyriboinosinic:polyribocytidylic acid and encephalomyocarditis picornavirus. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[54]  A. Lee,et al.  Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[55]  S. Nishikawa,et al.  Indispensable role of Bcl2 in the development of the melanocyte stem cell. , 2006, Developmental biology.

[56]  Zhijian J. Chen,et al.  Antiviral innate immunity pathways , 2006, Cell Research.

[57]  W. Pavan,et al.  Genetic evidence does not support direct regulation of EDNRB by SOX10 in migratory neural crest and the melanocyte lineage , 2006, Mechanisms of Development.

[58]  G. Kochs,et al.  The interferon response circuit: Induction and suppression by pathogenic viruses , 2005, Virology.

[59]  M. Khaled,et al.  The cleavage of microphthalmia-associated transcription factor, MITF, by caspases plays an essential role in melanocyte and melanoma cell apoptosis. , 2005, Genes & development.

[60]  D. Fisher,et al.  Mechanisms of Hair Graying: Incomplete Melanocyte Stem Cell Maintenance in the Niche , 2005, Science.

[61]  M. Tsai,et al.  Mast cells in the development of adaptive immune responses , 2005, Nature Immunology.

[62]  N. Copeland,et al.  Melanocytes and the microphthalmia transcription factor network. , 2004, Annual review of genetics.

[63]  T. Hirano,et al.  Roles of MITF for development of mast cells in mice: effects on both precursors and tissue environments. , 2004, Blood.

[64]  S. Ramaswamy,et al.  MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma. , 2003, The American journal of pathology.

[65]  E. Morii,et al.  Effect of Anatomical Distribution of Mast Cells on Their Defense Function against Bacterial Infections , 2003, The Journal of experimental medicine.

[66]  O. Moro,et al.  Involvement of microphthalmia-associated transcription factor (MITF) in expression of human melanocortin-1 receptor (MC1R). , 2002, Life sciences.

[67]  L. Chin,et al.  p16(Ink4a) in melanocyte senescence and differentiation. , 2002, Journal of the National Cancer Institute.

[68]  R Paus,et al.  A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. , 2001, The Journal of investigative dermatology.

[69]  E. Morii,et al.  Importance of leucine zipper domain of mi transcription factor (MITF) for differentiation of mast cells demonstrated using mi(ce)/mi(ce) mutant mice of which MITF lacks the zipper domain. , 2001, Blood.

[70]  B. Gilchrest,et al.  SCF/c‐kit signaling is required for cyclic regeneration of the hair pigmentation unit , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[71]  G. Erf,et al.  Herpesvirus connection in the expression of autoimmune vitiligo in Smyth line chickens. , 2001, Pigment cell research.

[72]  W. Pavan,et al.  Transcription factor hierarchy in Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3 , 2000, Human Genetics.

[73]  Stephen L. Johnson,et al.  nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate. , 1999, Development.

[74]  E. Price,et al.  α-Melanocyte-stimulating Hormone Signaling Regulates Expression of microphthalmia, a Gene Deficient in Waardenburg Syndrome* , 1998, The Journal of Biological Chemistry.

[75]  W. Pavan,et al.  Melanocyte development in vivo and in neural crest cell cultures: crucial dependence on the Mitf basic-helix-loop-helix-zipper transcription factor. , 1997, Development.

[76]  K Takahashi,et al.  Functional Analysis of Microphthalmia-associated Transcription Factor in Pigment Cell-specific Transcription of the Human Tyrosinase Family Genes* , 1997, The Journal of Biological Chemistry.

[77]  T. Kondo,et al.  Involvement of transcription factor encoded by the mi locus in the expression of c-kit receptor tyrosine kinase in cultured mast cells of mice. , 1996, Blood.

[78]  C. Goding,et al.  Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator , 1994, Molecular and cellular biology.

[79]  J. Fex,et al.  Cochlear disorder associated with melanocyte anomaly in mice with a transgenic insertional mutation , 1992, Molecular and Cellular Neuroscience.

[80]  H. Morse,et al.  Greying with age in mice: relation to expression of murine leukemia viruses , 1985, Cell.

[81]  R. Jaenisch,et al.  Chromosomal position and activation of retroviral genomes inserted into the germ line of mice , 1981, Cell.

[82]  Rudolf Jaenisch,et al.  Retroviruses and embryogenesis: Microinjection of Moloney leukemia virus into midgestation mouse embryos , 1980, Cell.

[83]  G. Merlino,et al.  Fluorescent protein-assisted purification for gene expression profiling. , 2011, Methods in molecular biology.

[84]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[85]  S. Locarnini,et al.  Toll-like receptors , RIG-Ilike RNA helicases and the antiviral innate immune response , 2007 .

[86]  L. Andersson,et al.  Avian models with spontaneous autoimmune diseases. , 2006, Advances in immunology.

[87]  N. Copeland,et al.  Interallelic complementation at the mouse Mitf locus. , 2003, Genetics.