Abstract
Hair is a defining mammalian feature that serves as a hallmark of human communication. Given the critical significance of hair in social, religious, and political contexts, it is important to understand factors that play a role in hair loss disorders. The hair follicle is an immune privileged site, and mounting evidence suggests that the collapse of immune privilege contributes to the pathogenesis of autoimmune hair loss disorders, including alopecia areata and lichen planopilaris. This review comprehensively appraises the current literature to shed light on mechanisms for immune privilege collapse, and examines the role of neurogenic stress in triggering this process.
References
1.
Sperling LC: Hair anatomy for the clinician. J Am Acad Dermatol 1991;25:1-17.
2.
Harries MJ: The immunopathobiology of lichen planopilaris; PhD thesis. Manchester, University of Manchester, 2011.
3.
Harries MJ, Paus R: The pathogenesis of primary cicatricial alopecias. Am J Pathol 2010;177:2152-2162.
4.
Paus R, Cotsarelis G: The biology of hair follicles. N Engl J Med 1999;341:491-497.
5.
Schneider MR, Schmidt-Ullrich R, Paus R: The hair follicle as a dynamic miniorgan. Curr Biol 2009;19:R132-R142.
6.
Meyer KC, Klatte JE, Dinh HV, Harries MJ, Reithmayer K, Meyer W, Sinclair R, Paus R: Evidence that the bulge region is a site of relative immune privilege in human hair follicles. Br J Dermatol 2008;159:1077-1085.
7.
Harries MJ, Trueb RM, Tosti A, Messenger AG, Chaudhry I, Whiting DA, Sinclair R, Griffiths CE, Paus R: How not to get scar(r)ed: pointers to the correct diagnosis in patients with suspected primary cicatricial alopecia. Br J Dermatol 2009;160:482-501.
8.
Ross EK, Tan E, Shapiro J: Update on primary cicatricial alopecias. J Am Acad Dermatol 2005;53:1-37.
9.
Kang H, Alzolibani AA, Otberg N, Shapiro J: Lichen planopilaris. Dermatol Ther 2008;21:249-256.
10.
Soares VC, Mulinari-Brenner F, Souza TE: Lichen planopilaris epidemiology: a retrospective study of 80 cases. An Bras Dermatol 2015;90:666-670.
11.
Meinhard J, Stroux A, Lünnemann L, Vogt A, Blume-Peytavi U: Lichen planopilaris: epidemiology and prevalence of subtypes - a retrospective analysis in 104 patients. J Dtsch Dermatol Ges 2014;12:229-235, 229-236.
12.
Handa S, Sahoo B: Childhood lichen planus: a study of 87 cases. Int J Dermatol 2002;41:423-427.
13.
Gilhar A, Paus R, Kalish RS: Lymphocytes, neuropeptides, and genes involved in alopecia areata. J Clin Invest 2007;117:2019-2027.
14.
Messenger AG, Slater DN, Bleehen SS: Alopecia areata: alterations in the hair growth cycle and correlation with the follicular pathology. Br J Dermatol 1986;114:337-347.
15.
Villasante Fricke AC, Miteva M: Epidemiology and burden of alopecia areata: a systematic review. Clin Cosmet Investig Dermatol 2015;8:397-403.
16.
Safavi KH, Muller SA, Suman VJ, Moshell AN, Melton LJ 3rd: Incidence of alopecia areata in Olmsted County, Minnesota, 1975 through 1989. Mayo Clin Proc 1995;70:628-633.
17.
Harries MJ, Meyer KC, Chaudhry IH, Griffiths CE, Paus R: Does collapse of immune privilege in the hair-follicle bulge play a role in the pathogenesis of primary cicatricial alopecia? Clin Exp Dermal 2010;35:637-644.
18.
Niederkorn JY: See no evil, hear no evil, do no evil: the lessons of immuneprivilege. Nat Immunol 2006;7:354-359.
19.
Hong S, Van Kaer L: Immune privilege: keeping an eye on natural killer T cells. J Exp Med 1999;190:1197-1200.
20.
Streilein JW, Ksander BR, Taylor AW: Immune deviation in relation to ocular immune privilege. J Immunol 1997;158:3557-3560.
21.
Streilein JW, Takeuchi M, Taylor AW: Immune privilege, T-cell tolerance, and tissue-restricted autoimmunity. Hum Immunol 1997;52:138-143.
22.
Ferguson TA, Griffith TS: A vision of cell death: insights into immune privilege. Immunol Rev 1997;156:167-184.
23.
Paus R, Ito N, Takigawa M, Ito T: The hair follicle and immune privilege. J Investig Dermatol Symp Proc 2003;8:188-194.
24.
Billingham RE: Transplantation immunity evoked by skin allografts and expressed in intact skin; in Montagna W, Billingham RE (eds): Immunology of the Skin. Adv Biol Skin. New York, Appleton-Century-Crofts, 1971, vol XI, pp 183-198.
25.
Billingham RE, Silvers WK: A biologist's reflections on dermatology. J Invest Dermatol 1971;57:227-240.
26.
Stenn KS, Paus R: Controls of hair follicle cycling. Physiol Rev 2001;81:449-494.
27.
Westgate GE, Craggs RI, Gibson WT: Immune privilege in hair growth. J Invest Dermatol 1991;97:417-420.
28.
Christoph T, Müller-Röver S, Audring H, Tobin DJ, Hermes B, Cotsarelis G, Rückert R, Paus R: The human hair follicle immune system: cellular composition and immune privilege. Br J Dermatol 2000;142:862-873.
29.
Bröcker EB, Echternacht-Happle K, Hamm H, Happle R: Abnormal expression of class I and class II major histocompatibility antigens in alopecia areata: modulation by topical immunotherapy. J Invest Dermatol 1987;88:564-568.
30.
Ito T, Ito N, Bettermann A, Tokura Y, Takigawa M, Paus R: Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model. Am J Pathol 2004;164, 623-634.
31.
Prasanna SJ, Nandi D: The MHC-encoded class I molecule, H-2Kk, demonstrates distinct requirements of assembly factors for cell surface expression: roles of TAP, Tapasin and beta2-microglobulin. Mol Immunol 2004;41:1029-1045.
32.
Paus R, Eichmüller S, Hofmann U, Czarnetzki BM, Robinson P: Expression of classical and non-classical MHC class I antigens in murine hair follicles. Br J Dermatol 1994;131:177-183.
33.
Rückert R, Hofmann U, van der Veen C, Bulfone-Paus S, Paus R: MHC class I expression in murine skin: developmentally controlled and strikingly restricted intraepithelial expression during hair follicle morphogenesis and cycling, and response to cytokine treatment in vivo. J Invest Dermatol 1998;111:25-30.
34.
Moseley RP, Brown JI, Auld J, Mumtaz H, Rainey AJ, Kirkham N, Gelsthorpe K, Masters R, Smith ME: An immunohistochemical study of MHC class I expression on human Langerhans cells and melanocytes. J Pathol 1997;181:419-425.
35.
Ito T, Ito N, Saatoff M, Hashizume H, Fukamizu H, Nickoloff BJ, Takigawa M, Paus R: Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack. J Invest Dermal 2008;128:1196-1206.
36.
Bröcker EB, Echternacht-Happle K, Hamm H, Happle R: Abnormal expression of class I and class II major histocompatibility antigens in alopecia areata: modulation by topical immunotherapy. J Invest Dermatol 1987;88:564-568.
37.
Braud VM, Allan DS, O'Callaghan CA, Söderström K, D'Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ: HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 1998;391:795-799.
38.
Ito T: Hair follicle is a target of stress hormone and autoimmune reactions. J Dermatol Sci 2010;60:67-73.
39.
Cerwenka A, Swain SL: TGF-beta1: immunosuppressant and viability factor for T lymphocytes. Microbes Infect 1999;1:1291-1296.
40.
Wahl SM, Wen J, Moutsopoulos N: TGF-beta: a mobile purveyor of immune privilege. Immunol Rev 2006;213:213-227.
41.
Foitzik K, Lindner G, Mueller-Roever S, Maurer M, Botchkareva N, Botchkarev V, Handjiski B, Metz M, Hibino T, Soma T, Dotto GP, Paus R: Control of murine hair follicle regression (catagen) by TGF-beta1 in vivo. FASEB J 2000;14:752-760.
42.
Paus R, Nickoloff BJ, Ito T: A “hairy” privilege. Trends Immunol 2005;26:32-40.
43.
Gilhar A, Kalish RS: Alopecia areata: a tissue specific autoimmune disease of the hair follicle. Autoimmun Rev 2006;5:64-69.
44.
Nishimura EK, Suzuki M, Igras V, Du J, Lonning S, Miyachi Y, Roes J, Beermann F, Fisher DE: Key roles for transforming growth factor beta in melanocyte stem cell maintenance. Cell Stem Cell 2010;6:130-140.
45.
Tanimura S, Tadokoro Y, Inomata K, Binh NT, Nishie W, Yamazaki S, Nakauchi H, Tanaka Y, McMillan JR, Sawamura D, Yancey K, Shimizu H, Nishimura EK: Hair follicle stem cells provide a functional niche for melanocyte stem cells. Cell Stem Cell 2011;8:177-187.
46.
Slominski A, Wortsman J, Mazurkiewicz JE, Matsuoka L, Dietrich J, Lawrence K, Gorbani A, Paus R: Detection of proopiomelanocortin-derived antigens in normal and pathologic human skin. J Lab Clin Med 1993;122:658-666.
47.
Slominski A, Botchkareva NV, Botchkarev VA, Chakraborty A, Luger T, Uenalan M, Paus R: Hair cycle-dependent production of ACTH in mouse skin. Biochim Biophys Acta 1998;1448:147-152.
48.
Slominski A, Wortsman J, Luger T, Paus R, Solomon S: Corticotropin releasing hormone and proopiomelanocortin involvement in the cutaneous response to stress. Physiol Rev 2000;80:979-1020.
49.
Slominski A, Paus R, Mazurkiewicz J: Proopiomelanocortin expression in the skin during induced hair growth in mice. Experientia 1992;48:50-54.
50.
Slominski A, Ermak G, Hwang J, Mazurkiewicz J, Corliss D, Eastman A: The expression of proopiomelanocortin (POMC) and of corticotropin releasing hormone receptor (CRH-R) genes in mouse skin. Biochim Biophys Acta 1996;1289:247-251.
51.
Slominski A, Botchkareva NV, Botchkarev VA, Chakraborty A, Luger T, Uenalan M, Paus R: ACTH production in C57BL/6 mouse skin. Ann NY Acad Sci 1999;885:448-450.
52.
Paus R, Botchkarev VA, Botchkareva NV, Mecklenburg L, Luger T, Slominski A: The skin POMC system (SPS). Leads and lessons from the hair follicle. Ann NY Acad Sci 1999;885:350-363.
53.
Slominski A, Heasley D, Mazurkiewicz JE, Ermak G, Baker J, Carlson JA: Expression of proopiomelanocortin (POMC)-derived melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) peptides in skin of basal cell carcinoma patients. Hum Pathol 1999;30:208-215.
54.
Luger TA, Scholzen T, Brzoska T, Becher E, Slominski A, Paus R: Cutaneous immunomodulation and coordination of skin stress responses by alpha-melanocyte-stimulating hormone. Ann NY Acad Sci 1998;840:381-394.
55.
Luger TA, Scholzen TE, Brzoska T, Böhm M: New insights into the functions of alpha-MSH and related peptides in the immune system. Ann NY Acad Sci 2003;994:133-140.
56.
Apte RS, Sinha D, Mayhew E, Wistow GJ, Niederkorn JY: Cutting edge: role of macrophage migration inhibitory factor in inhibiting NK cell activity and preserving immune privilege. J Immunol 1998;160:5693-5696.
57.
Arcuri F, Cintorino M, Carducci A, Papa S, Riparbelli MG, Mangioni S, Di Blasio AM, Tosi P, Viganò P: Human decidual natural killer cells as a source and target of macrophage migration inhibitory factor. Reproduction 2006;131:175-182.
58.
Ohyama M, Terunuma A, Tock CL, Radonovich MF, Pise-Masison CA, Hopping SB, Brady JN, Udey MC, Vogel JC: Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest 2006;116:249-260.
59.
Barclay AN, Wright GJ, Brooke G, Brown MH: CD200 and membrane protein interactions in the control of myeloid cells. Trends Immunol 2002;23:285-290.
60.
Rosenblum MD, Olasz EB, Yancey KB, Woodliff JE, Lazarova Z, Gerber KA, Truitt RL: Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance? J Invest Dermatol 2004;123:880-887.
61.
Rosenblum MD, Yancey KB, Olasz EB, Truitt RL: CD200, a “no danger” signal for hair follicles. J Dermatol Sci 2006;41:165-174.
62.
Apte RS, Niederkorn JY: Isolation and characterization of a unique natural killer cell inhibitory factor present in the anterior chamber of the eye. J Immunol 1996;156:2667-2673.
63.
Harries MJ, Meyer K, Chaudhry I, E Kloepper J, Poblet E, Griffiths CE, Paus R: Lichen planopilaris is characterized by immune privilege collapse of the hair follicle's epithelial stem cell niche. J Pathol 2013;231:236-247.
64.
Paus R, Slominski A, Czarnetzki BM: Is alopecia areata an autoimmune-response against melanogenesis-related proteins, exposed by abnormal MHC class I expression in the anagen hair bulb? Yale J Biol Med 1993;66:541-554.
65.
Freyschmidt-Paul P, McElwee KJ, Hoffmann R, et al: Interferon-gamma-deficient mice are resistant to the development of alopecia areata. Br J Dermatol 2006;155:515-521.
66.
Cotsarelis G: Gene expression profiling gets to the root of human hair follicle stem cells. J Clin Invest 2006;116:19-22.
67.
Tiede S, Koop N, Kloepper JE, Fässler R, Paus R: Nonviral in situ green fluorescent protein labeling and culture of primary, adult human hair follicle epithelial progenitor cells. Stem Cells 2009;27:2793-2803.
68.
Stelekati E, Bahri R, D'Orlando O, Orinska Z, Mittrücker HW, Langenhaun R, Glatzel M, Bollinger A, Paus R, Bulfone-Paus S: Mast cell-mediated antigen presentation regulates CD8+ T cell effector functions. Immunity 2009;31:665-676.
69.
Groh V, Bahram S, Bauer S, Herman A, Beauchamp M, Spies T: Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci USA 1996;93:12445-12450.
70.
Yamamoto K, Fujiyama Y, Andoh A, Bamba T, Okabe H: Oxidative stress increases MICA and MICB gene expression in the human colon carcinoma cell line (CaCo-2). Biochim Biophys Acta 2001;1526:10-12.
71.
Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T: Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 1999;285:727-729.
72.
Carosella ED, Rouas-Freiss N, Paul P, Dausset J: HLA-G: a tolerance molecule from the major histocompatibility complex. Immunol Today 1999;20:60-62.
73.
Wu J, Song Y, Bakker AB, et al: An activating immunoreceptor complex formed by NKG2D and DAP10. Science 1999;285:730-732.
74.
Menier C, Riteau B, Carosella ED, Rouas-Freiss N: MICA triggering signal for NK cell tumor lysis is counteracted by HLA-G1-mediated inhibitory signal. Int J Cancer 2002;100:63-70.
75.
Middleton D, Curran M, Maxwell L: Natural killer cells and their receptors. Transpl Immunol 2002;10:147-164.
76.
Pende D, Rivera P, Marcenaro S, Chang CC, Biassoni R, Conte R, Kubin M, Cosman D, Ferrone S, Moretta L, Moretta A: Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Cancer Res 2002;62:6178-6186.
77.
Groh V, Bruhl A, El-Gabalawy H, Nelson JL, Spies T: Stimulation of T cell autoreactivity by anomalous expression of NKG2D and its MIC ligands in rheumatoid arthritis. Proc Natl Acad Sci USA 2003;100:9452-9457.
78.
Caillat-Zucman S: How NKG2D ligands trigger autoimmunity? Hum Immunol 2006;67:204-207.
79.
Jie HB, Sarvetnick N: The role of NK cells and NK cell receptors in autoimmune disease. Autoimmunity 2004;37:147-153.
80.
Shoenfeld Y, Isenberg DA: The mosaic of autoimmunity. Immunol Today 1989;10:123-126.
81.
Brickman CM, Shoenfeld Y: The mosaic of autoimmunity. Scand J Clin Lab Invest Suppl 2001;235:3-15.
82.
Herrmann M, Schölmerich J, Straub RH: Stress and rheumatic diseases. Rheum Dis Clin North Am 2000;26:737-763.
83.
Stojanovich L: Stress and autoimmunity. Autoimmun Rev 2010;9:A271-A276.
84.
Shepshelovich D, Shoenfeld Y: Prediction and prevention of autoimmune diseases: additional aspects of the mosaic of autoimmunity. Lupus 2006;15:183-190.
85.
Huerta PT, Kowal C, DeGiorgio LA, Volpe BT, Diamond B: Immunity and behavior: antibodies alter emotion. Proc Natl Acad Sci USA 2006;103:678-83.
86.
Brauner GJ, Goodheart HP: Dermatologic care behind bars. J Am Acad Dermatol 1988;18:1066-1073.
87.
Muller SA, Winkelmann RK: Alopecia areata: an evaluation of 736 patients. Arch Dermatol 1963;88:290-297.
88.
Chrousos GP: The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 1995;332:1351-1362.
89.
García-Hernández MJ, Ruiz-Doblado S, Rodriguez-Pichardo A, Camacho F: Alopecia areata, stress and psychiatric disorders: a review. J Dermatol 1999;26:625-632.
90.
Inui S, Nakajima T, Itami S: Two cases of alopecia areata responsive to fexofenadine. J Dermatol 2007;34:852-854.
91.
Kakourou T, Karachristou K, Chrousos G: A case series of alopecia areata in children: impact of personal and family history of stress and autoimmunity. J Eur Acad Dermatol Venereol 2007;21:356-359.
92.
Hampf BG, Malmström MJ, Aalberg VA, Hannula JA, Vikkula J: Psychiatric disturbance in patients with oral lichen planus. Oral Surg Oral Med Oral Pathol 1987;63:429-432.
93.
Kaplan B, Barnes L: Oral lichen planus and squamous carcinoma. Case report and update of the literature. Arch Otolaryngol 1985;111:543-547.
94.
Lowental U, Pisanti S: Oral lichen planus according to the modern medical model. J Oral Med 1984;39:224-226.
95.
Boyd AS, Neldner KH: Lichen planus. J Am Acad Dermatol 1991;25:593-619.
96.
Ito N, Ito T, Kromminga A, Bettermann A, Takigawa M, Kees F, Straub RH, Paus R: Human hair follicles display a functional equivalent of the hypothalamic-pituitary-adrenal axis and synthesize cortisol. FASEB J 2005;19:1332-1334.
97.
Arck PC, Handjiski B, Peters EM, Peter AS, Hagen E, Fischer A, Klapp BF, Paus R: Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways. Am J Pathol 2003;162:803-814.
98.
Roloff B, Fechner K, Slominski A, Furkert J, Botchkarev VA, Bulfone-Paus S, Zipper J, Krause E, Paus R: Hair cycle-dependent expression of corticotropin-releasing factor (CRF) and CRF receptors in murine skin. FASEB J 1998;12:287-297.
99.
Slominski A, Pisarchik A, Tobin DJ, Mazurkiewicz JE, Wortsman J: Differential expression of a cutaneous corticotropin-releasing hormone system. Endocrinology 2004;145:941-950.
100.
Ito N, Ito T, Betterman A, Paus R: The human hair bulb is a source and target of CRH. J Invest Dermal 2004;122:235-237.
101.
Ito N, Sugawara K, Bodó E, Takigawa M, van Beek N, Ito T, Paus R: Corticotropin-releasing hormone stimulates the in-situ generation of mast cells from precursors in the human hair follicle mesenchyme. J Invest Dermatol 2010;130:995-1004.
102.
Maurer M, Echtenacher B, Hültner L, Kollias G, Männel DN, Langley KE, Galli SJ: The c-kit ligand, stem cell factor, can enhance innate immunity through effects on mast cells. J Exp Med 1998;188:2343-2348.
103.
Weber A, Knop J, Maurer M: Pattern analysis of human cutaneous mast cell populations by total body surface mapping. Br J Dermatol 2003;148:224-228.
104.
Theoharides TC, Cochrane DE: Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol 2004;146:1-12.
105.
Arck PC, Handjiski B, Kuhlmei A, Peters EM, Knackstedt M, Peter A, Hunt SP, Klapp BF, Paus R: Mast cell deficient and neurokinin-1 receptor knockout mice are protected from stress-induced hair growth inhibition. J Mol Med (Berl) 2005;83:386-396.
106.
Maurer M, Metz M: The status quo and quo vadis of mast cells. Exp Dermatol 2005;14:923-929.
107.
Weller K, Foitzik K, Paus R, Syska W, Maurer M: Mast cells are required for normal healing of skin wounds in mice. FASEB J 2006;20:2366-2368.
108.
Metz M, Maurer M: Mast cells-key effector cells in immune responses. Trends Immunol 2007;28:234-241.
109.
Arck PC, Handjiski B, Hagen E, Joachim R, Klapp BF, Paus R: Indications for a “brain-hair follicle axis (BHA)”: inhibition of keratinocyte proliferation and up-regulation of keratinocyte apoptosis in telogen hair follicles by stress and substance P. FASEB J 2001;15:2536-2538.
110.
Theoharides TC, Singh LK, Boucher W, et al: Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects. Endocrinology 1998;139:403-413.
111.
Theoharides TC, Donelan JM, Papadopoulou N, Cao J, Kempuraj D, Conti P: Mast cells as targets of corticotropin-releasing factor and related peptides. Trends Pharmacol Sci 2004;25:563-568.
112.
Maurer M, Theoharides T, Granstein RD, et al: What is the physiological function of mast cells? Exp Dermatol 2003;12:886-910.
113.
Aloe L, Alleva E, Böhm A, Levi-Montalcini R: Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream. Proc Natl Acad Sci USA 1986;83:6184-6187.
114.
Aloe L, Alleva E, De Simone R: Changes of NGF level in mouse hypothalamus following intermale aggressive behaviour: biological and immunohistochemical evidence. Behav Brain Res 1990;39:53-61.
115.
Tron VA, Coughlin MD, Jang DE, Stanisz J, Sauder DN: Expression and modulation of nerve growth factor in murine keratinocytes (PAM 212). J Clin Invest 1990;85:1085-1089.
116.
Paus R, Luftl M, Czarnetzki BM: Nerve growth factor modulates keratinocyte proliferation in murine skin organ culture. Br J Dermatol 1994;130:174-180.
117.
Botchkarev VA, Welker P, Albers KM, et al: A new role for neurotrophin-3:involvement in the regulation of hair follicle regression (catagen). Am J Pathol 1998;153:785-799.
118.
Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV: Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature 1996;383:716-719.
119.
Frade JM, Rodriguez Tebar A, Barde YA: Induction of cell death by endogenous nerve growth factor through its p75 receptor. Nature 1996;383:166-168.
120.
Yaar M, Zhai S, Pilch PF, et al: Binding of β-amyloid to the p75 neurotrophin receptor induces apoptosis: a possible mechanism for Alzheimer's disease. J Clin Invest 1997;100:2333-2340.
121.
Peters EM, Handjiski B, Kuhlmei A, Hagen E, Bielas H, Braun A, Klapp BF, Paus R, Arck PC: Neurogenic inflammation in stress-induced termination of murine hair growth is promoted by nerve growth factor. Am J Pathol 2004;165:259-271.
122.
Botchkareva NV, Botchkarev VA, Chen LH, Lindner G, Paus R: A role for p75 neurotrophin receptor in the control of hair follicle morphogenesis. Dev Biol 1999;216:135-153.
123.
Marshall JS, Gomi K, Blennerhassett MG, Bienenstock J: Nerve growth factor modifies the expression of inflammatory cytokines by mast cells via a prostanoid-dependent mechanism. J Immunol 1999;162:4271-4276.
124.
Peters EM, Liotiri S, Bodó E, Hagen E, Bíró T, Arck PC, Paus R: Probing the effects of stress mediators on the human hair follicle: substance P holds central position. Am J Pathol 2007;171:1872-1886.
125.
Singh LK, Pang X, Alexacos N, Letourneau R, Theoharides TC: Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin, and substance P: a link to neurogenic skin disorders. Brain Behav Immun 1999;13:225-239.
126.
Scholzen T, Armstrong CA, Bunnett NW, Luger TA, Olerud JE, Ansel JC: Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems. Exp Dermatol 1998;7:81-96.
127.
Ansel JC, Brown JR, Payan DG, Brown MA: Substance P selectively activates TNF-alpha gene expression in murine mast cells. J Immunol 1993;150:4478-4485.
128.
Hoffmann R, Eicheler W, Huth A, Wenzel E, Happle R: Cytokines and growth factors influence hair growth in vitro. Possible implications for the pathogenesis and treatment of alopecia areata. Arch Dermatol Res 1996;288:153-156.
129.
Bläsing H, Hendrix S, Paus R: Pro-inflammatory cytokines upregulate the skin immunoreactivity for NGF, NT-3, NT-4 and their receptor, p75NTR in vivo: a preliminary report. Arch Dermatol Res 2005;296:580-584.
130.
Tong X, Coulombe PA: Keratin 17 modulates hair follicle cycling in a TNF alpha-dependent fashion. Genes Dev 2006;20:1353-1364.
131.
Arck PC, Slominski A, Theoharides TC, Peters EM, Paus R: Neuroimmunology of stress: skin takes center stage. J Invest Dermatol 2006;126:1697-1704.
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