Epidermal EGFR controls cutaneous host defense and prevents inflammation

Science Translational Medicine

Volumn 5, Issue 199, 2013, Pages

  Lichtenberger, Beate M ^a,e   Gerber, Peter A ^b   Holcmann, Martin ^a   Buhren, Bettina A ^b   Amberg, Nicole ^a   Smolle, Viktoria ^a   Schrumpf, Holger ^b   Boelke, Edwin ^b   Ansari, Parinaz ^b   Mackenzie, Colin ^b   Wollenberg, Andreas ^c   Kislat, Andreas ^b   Fischer, Jens W ^b   Röck, Katharina ^b   Harder, Jürgen ^d   Schröder, Jens M ^d   Homey, Bernhard ^b   Sibilia, Maria ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b HEINRICH HEINE UNIVERSITY   (Germany)

^c UNIVERSITY OF MUNICH   (Germany)

^d UNIVERSITY HOSPITAL SCHLESWIG HOLSTEIN   (Germany)

^e KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFLAMMATORY AGENT; CETUXIMAB; CUTANEOUS T CELL ATTRACTING CHEMOKINE; CXCL14 CHEMOKINE; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; MAST CELL INHIBITOR; MONOCYTE CHEMOTACTIC PROTEIN 1; MYELOID DIFFERENTIATION FACTOR 88; POLYPEPTIDE ANTIBIOTIC AGENT; RAG2 PROTEIN; RANTES; REGULATOR PROTEIN; SKIN BARRIER PROTEIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL INFILTRATION; CONTROLLED STUDY; CYTOTOXICITY; DEGENERATION; DENDRITIC CELL; DERMATITIS; DRUG ERUPTION; EPIDERMIS; GRANULOCYTE; HAIR FOLLICLE; HOST RESISTANCE; HUMAN; HUMAN CELL; HUMAN TISSUE; INFLAMMATION; KERATINOCYTE; LANGERHANS CELL; LETHALITY; LYMPHOCYTE; LYMPHOCYTE MIGRATION; MACROPHAGE; MAJOR CLINICAL STUDY; MAST CELL; MOUSE; NONHUMAN; PAPULOPUSTULAR RASH; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SYNTHESIS; SIGNAL TRANSDUCTION; SKIN TOXICITY; STAPHYLOCOCCUS AUREUS; T LYMPHOCYTE;

ANIMALS; ANTINEOPLASTIC AGENTS; CHEMOKINES; CYTOKINES; DERMATITIS; EXANTHEMA; HAIR FOLLICLE; HUMANS; INFLAMMATION MEDIATORS; INTERLEUKIN-1; KERATINOCYTES; LANGERHANS CELLS; LYMPHOCYTES; MALE; MICE; MICE, 129 STRAIN; MICE, INBRED C57BL; MICE, KNOCKOUT; MIDDLE AGED; NEOPLASMS; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; SKIN; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84883890133     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3005886     Document Type: Article

References (54)

1. J. Schlessinger, Ligand-induced, receptor-mediated dimerization and activation of EGF receptor. Cell 110, 669-672 (2002).
2. M. Sibilia, R. Kroismayr, B. M. Lichtenberger, A. Natarajan, M. Hecking, M. Holcmann, The epidermal growth factor receptor: From development to tumorigenesis. Differentiation 75, 770-787 (2007).
3. M. Sibilia, E. F. Wagner, Strain-dependent epithelial defects in mice lacking the EGF receptor. Science 269, 234-238 (1995).
4. M. A. Olayioye, R. M. Neve, H. A. Lane, N. E. Hynes, The ErbB signaling network: Receptor heterodimerization in development and cancer. EMBO J. 19, 3159-3167 (2000).
5. B. M. Lichtenberger, P. K. Tan, H. Niederleithner, N. Ferrara, P. Petzelbauer, M. Sibilia, Autocrine VEGF signaling synergizes with EGFR in tumor cells to promote epithelial cancer development. Cell 140, 268-279 (2010).
6. M. Sibilia, A. Fleischmann, A. Behrens, L. Stingl, J. Carroll, F. M. Watt, J. Schlessinger, E. F. Wagner, The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development. Cell 102, 211-220 (2000).
7. F. Ciardiello, G. Tortora, EGFR antagonists in cancer treatment. N. Engl. J. Med. 358, 1160-1174 (2008).
8. R. E. Eilers Jr., M. Gandhi, J. D. Patel, M. F. Mulcahy, M. Agulnik, T. Hensing, M. E. Lacouture, Dermatologic infections in cancer patients treated with epidermal growth factor receptor inhibitor therapy. J. Natl. Cancer Inst. 102, 47-53 (2010).
9. M. E. Lacouture, Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat. Rev. Cancer 6, 803-812 (2006).
10. B. Wacker, T. Nagrani, J. Weinberg, K. Witt, G. Clark, P. J. Cagnoni, Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. Clin. Cancer Res. 13, 3913-3921 (2007).
11. F. Mascia, V. Mariani, G. Girolomoni, S. Pastore, Blockade of the EGF receptor induces a deranged chemokine expression in keratinocytes leading to enhanced skin inflammation. Am. J. Pathol. 163, 303-312 (2003).
12. T. Grenader, M. Gipps, A. Goldberg, Staphylococcus aureus bacteremia secondary to severe erlotinib skin toxicity. Clin. Lung Cancer 9, 59-60 (2008).
13. I. F. Charo, R. M. Ransohoff, The many roles of chemokines and chemokine receptors in inflammation. N. Engl. J. Med. 354, 610-621 (2006).
14. B. Homey, H. Alenius, A. Müller, H. Soto, E. P. Bowman, W. Yuan, L. McEvoy, A. I. Lauerma, T. Assmann, E. Bünemann, M. Lehto, H. Wolff, D. Yen, H. Marxhausen, W. To, J. Sedgwick, T. Ruzicka, P. Lehmann, A. Zlotnik, CCL27-CCR10 interactions regulate T cell-mediated skin inflammation. Nat. Med. 8, 157-165 (2002).
15. A. Müller, B. Homey, H. Soto, N. Ge, D. Catron, M. E. Buchanan, T. McClanahan, E. Murphy, W. Yuan, S. N. Wagner, J. L. Barrera, A. Mohar, E. Verástegui, A. Zlotnik, Involvement of chemokine receptors in breast cancer metastasis. Nature 410, 50-56 (2001).
16. T. Kakinuma, H. Saeki, Y. Tsunemi, H. Fujita, N. Asano, H. Mitsui, Y. Tada, M. Wakugawa, T. Watanabe, H. Torii, M. Komine, A. Asahina, K. Nakamura, K. Tamaki, Increased serum cutaneous T cell-attracting chemokine (CCL27) levels in patients with atopic dermatitis and psoriasis vulgaris. J. Allergy Clin. Immunol. 111, 592-597 (2003).
17. J. Nakazato, M. Kishida, R. Kuroiwa, J. Fujiwara, M. Shimoda, N. Shinomiya, Serum levels of Th2 chemokines, CCL17, CCL22, and CCL27, were the important markers of severity in infantile atopic dermatitis. Pediatr. Allergy Immunol. 19, 605-613 (2008).
18. J. Harder, J. Bartels, E. Christophers, J. M. Schröder, A peptide antibiotic from human skin. Nature 387, 861 (1997).
19. J. Harder, J. M. Schroder, RNase 7, a novel innate immune defense antimicrobial protein of healthy human skin. J. Biol. Chem. 277, 46779-46784 (2002).
20. J. M. Schröder, J. Harder, Antimicrobial skin peptides and proteins. Cell. Mol. Life Sci. 63, 469-486 (2006).
21. A. Natarajan, B. Wagner, M. Sibilia, The EGF receptor is required for efficient liver regeneration. Proc. Natl. Acad. Sci. U.S.A. 104, 17081-17086 (2007).
22. P. A. Gerber, B. A. Buhren, F. Cevikbas, E. Bölke, M. Steinhoff, B. Homey, Preliminary evidence for a role of mast cells in epidermal growth factor receptor inhibitor-induced pruritus. J. Am. Acad. Dermatol. 63, 163-165 (2010).
23. M. Sibilia, B. Wagner, A. Hoebertz, C. Elliott, S. Marino, W. Jochum, E. F. Wagner, Mice humanised for the EGF receptor display hypomorphic phenotypes in skin, bone and heart. Development 130, 4515-4525 (2003).
24. P. A. Gerber, B. Homey, Images in clinical medicine. Erlotinib-induced hair alterations. N. Engl. J. Med. 358, 1175 (2008).
25. T. Christoph, S. Müller-Röver, H. Audring, D. J. Tobin, B. Hermes, G. Cotsarelis, R. Rückert, R. Paus, The human hair follicle immune system: Cellular composition and immune privilege. Br. J. Dermatol. 142, 862-873 (2000).
26. M. V. Brancaz, R. Iratni, A. Morrison, S. J. Mancini, P. Marche, J. Sundberg, S. Nonchev, A new allele of the mouse hairless gene interferes with Hox/LacZ transgene regulation in hair follicle primordia. Exp. Mol. Pathol. 76, 173-181 (2004).
27. Y. Shinkai, G. Rathbun, K. P. Lam, E. M. Oltz, V. Stewart, M. Mendelsohn, J. Charron, M. Datta, F. Young, A. M. Stall, F. W. Alt, RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell 68, 855-867 (1992).
28. A. Kissenpfennig, S. Henri, B. Dubois, C. Laplace-Builhé, P. Perrin, N. Romani, C. H. Tripp, P. Douillard, L. Leserman, D. Kaiserlian, S. Saeland, J. Davoust, B. Malissen, Dynamics and function of Langerhans cells in vivo: Dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22, 643-654 (2005).
29. U. Rodeck, Skin toxicity caused by EGFR antagonists-An autoinflammatory condition triggered by deregulated IL-1 signaling? J. Cell. Physiol. 218, 32-34 (2009).
30. O. Adachi, T. Kawai, K. Takeda, M. Matsumoto, H. Tsutsui, M. Sakagami, K. Nakanishi, S. Akira, Targeted disruption of the MyD88 gene results in loss of IL-1-and IL-18-mediated function. Immunity 9, 143-150 (1998).
31. M. S. Kim, D. H. Lee, C. W. Lee, Y. K. Kim, M. J. Lee, C. Y. Shin, K. H. Cho, J. H. Chung, Mast cell stabilizer, ketotifen, prevents UV-induced wrinkle formation. J. Invest. Dermatol. 133, 1104-1107 (2013).
32. V. Liu, D. A. White, M. F. Zakowski, W. Travis, M. G. Kris, M. S. Ginsberg, V. A. Miller, C. G. Azzoli, Pulmonary toxicity associated with erlotinib. Chest 132, 1042-1044 (2007).
33. R. S. Herbst, A. M. Maddox, M. L. Rothenberg, E. J. Small, E. H. Rubin, J. Baselga, F. Rojo, W. K. Hong, H. Swaisland, S. D. Averbuch, J. Ochs, P. M. LoRusso, Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: Results of a phase I trial. J. Clin. Oncol. 20, 3815-3825 (2002).
34. C. Giro, B. Berger, E. Bölke, I. F. Ciernik, F. Duprez, L. Locati, S. Maillard, M. Ozsahin, R. Pfeffer, A. G. Robertson, J. A. Langendijk, W. Budach, High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: Results of a survey in EORTC institutes. Radiother. Oncol. 90, 166-171 (2009).
35. S. Pastore, F. Mascia, V. Mariani, G. Girolomoni, The epidermal growth factor receptor system in skin repair and inflammation. J. Invest. Dermatol. 128, 1365-1374 (2008).
36. M. P. Zorzou, A. Stratigos, E. Efstathiou, A. Bamias, Exacerbation of psoriasis after treatment with an EGFR tyrosine kinase inhibitor. Acta Derm. Venereol. 84, 308-309 (2004).
37. S. Meuter, B. Moser, Constitutive expression of CXCL14 in healthy human and murine epithelial tissues. Cytokine 44, 248-255 (2008).
38. I. Kurth, K. Willimann, P. Schaerli, T. Hunziker, I. Clark-Lewis, B. Moser, Monocyte selectivity and tissue localization suggests a role for breast and kidney-expressed chemokine (BRAK) in macrophage development. J. Exp. Med. 194, 855-861 (2001).
39. G. V. Shurin, R. L. Ferris, I. L. Tourkova, L. Perez, A. Lokshin, L. Balkir, B. Collins, G. S. Chatta, M. R. Shurin, Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration by dendritic cells (DC), while restoration of human CXCL14 expression in tumor cells causes attraction of DC both in vitro and in vivo. J. Immunol. 174, 5490-5498 (2005).
40. T. W. Song, M. H. Sohn, E. S. Kim, K. W. Kim, K. E. Kim, Increased serum thymus and activation-regulated chemokine and cutaneous T cell-attracting chemokine levels in children with atopic dermatitis. Clin. Exp. Allergy 36, 346-351 (2006).
41. A. Pivarcsi, A. Müller, A. Hippe, J. Rieker, A. van Lierop, M. Steinhoff, S. Seeliger, R. Kubitza, U. Pippirs, S. Meller, P. A. Gerber, R. Liersch, E. Buenemann, E. Sonkoly, U. Wiesner, T. K. Hoffmann, L. Schneider, R. Piekorz, E. Enderlein, J. Reifenberger, U. P. Rohr, R. Haas, P. Boukamp, I. Haase, B. Nürnberg, T. Ruzicka, A. Zlotnik, B. Homey, Tumor immune escape by the loss of homeostatic chemokine expression. Proc. Natl. Acad. Sci. U.S.A. 104, 19055-19060 (2007).
42. J. A. Bonner, P. M. Harari, J. Giralt, R. B. Cohen, C. U. Jones, R. K. Sur, D. Raben, J. Baselga, S. A. Spencer, J. Zhu, H. Youssoufian, E. K. Rowinsky, K. K. Ang, Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-Year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 11, 21-28 (2010).
43. T. C. Lee, D. W. Threadgill, Generation and validation of mice carrying a conditional allele of the epidermal growth factor receptor. Genesis 47, 85-92 (2009).
44. C. W. Franzke, C. Cobzaru, A. Triantafyllopoulou, S. Löffek, K. Horiuchi, D. W. Threadgill, T. Kurz, N. van Rooijen, L. Bruckner-Tuderman, C. P. Blobel, Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand-dependent terminal keratinocyte differentiation. J. Exp. Med. 209, 1105-1119 (2012).
45. B. B. Aggarwal, Signalling pathways of the TNF superfamily: A double-edged sword. Nat. Rev. Immunol. 3, 745-756 (2003).
46. L. L. Moldawer, E. M. Copeland III, Proinflammatory cytokines, nutritional support, and the cachexia syndrome: Interactions and therapeutic options. Cancer 79, 1828-1839 (1997).
47. F. Mascia, G. Lam, C. Keith, C. Garber, S. M. Steinberg, E. Kohn, S. H. Yuspa, Genetic ablation of epidermal EGFR reveals the dynamic origin of adverse effects of anti-EGFR therapy. Sci. Transl. Med. 5, 199ra110 (2013).
48. P. A. Gerber, E. Enderlein, B. Homey, The Koebner-phenomenon in epidermal growth factor receptor inhibitor-induced cutaneous adverse effects. J. Clin. Oncol. 26, 2790-2792 (2008).
49. J. Harder, J. Bartels, E. Christophers, J. M. Schroder, Isolation and characterization of human b-defensin-3, a novel human inducible peptide antibiotic. J. Biol. Chem. 276, 5707-5713 (2001).
50. J. Harder, R. Gläser, J. M. Schröder, Human antimicrobial proteins effectors of innate immunity. J. Endotoxin Res. 13, 317-338 (2007).
51. O. E. Sørensen, J. B. Cowland, K. Theilgaard-Mönch, L. Liu, T. Ganz, N. Borregaard, Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J. Immunol. 170, 5583-5589 (2003).
52. B. Köten, M. Simanski, R. Gläser, R. Podschun, J. M. Schröder, J. Harder, RNase 7 contributes to the cutaneous defense against Enterococcus faecium . PLoS One 4, e6424 (2009).
53. B. Lu, B. J. Rutledge, L. Gu, J. Fiorillo, N. W. Lukacs, S. L. Kunkel, R. North, C. Gerard, B. J. Rollins, Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J. Exp. Med. 187, 601-608 (1998).
54. B. M. Lichtenberger, P. A. Gerber, M. Holcmann, B. A. Buhren, N. Amberg, V. Smolle, H. Schrumpf, E. Boelke, P. Ansari, C. Mackenzie, A. Wollenberg, A. Kislat, J. W. Fischer, K. Röck, J. Harder, J. M. Schröder, B. Homey, M. Sibilia, Epidermal EGFR controls cutaneous host defense and prevents inflammation. Sci. Transl. Med. 5, 199ra111 (2013).