Lymphocytic Expression of Fas and FasL Apoptotic Markers in Vitiligo
Clinical Medicine Research
Volume 2, Issue 5, September 2013, Pages: 105-109
Received: Aug. 24, 2013; Published: Sep. 20, 2013
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Authors
Fatma Y. Saleh, Department of Dermatology and Venereology, Faculty of Medicine, Minia University, Egypt
Sherif Shoukry Awad, Department of Dermatology and Venereology, Faculty of Medicine, Minia University, Egypt
Irene M. Sadek, Department of Dermatology and Venereology, Faculty of Medicine, Minia University, Egypt
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Abstract
Background. Lymphocytic dermal infiltrations accompany the melanocytes loss in depigmenting vitiligo skin. These lymphocytes are incriminated during the pathogenesis of the disease. Fas receptor is a death receptor on the surface of cells that leads to programmed cell death (apoptosis) and FasL is its ligand. Fas/FasL system plays a crucial role in modulating apoptosis. Objectives. This study investigates the lymphocytic expression of apoptotic markers Fas/FasL in vitiligo. Methods. The present study was conducted on 45 vitiligo samples obtained from 15 vitiligo patients including 8 females (53.3%) and seven males (46.7%). Biopsies were obtained also from control volunteers. All specimens were routinely stained with Hematoxylin &Eosin and immunohistochemically for Fas & FasL apoptotic markers. Results. Fas & FasL were significantly expressed by infiltrating lymphocytes in vitiligo biopsies compared to control. Lymphocytic expression of Fas & FasL was higher on the edge biopsies than the center. Considerable lymphocytic infiltration and attack of B.M. were associated with higher lymphocytic Fas and FasL expression. During vitiligo activity lymphocytic Fas & FasL expression was also significantly higher. Conclusions. Lymphocytic Fas and FasL are significantly expressed in vitiligo patches which may trigger epidermal apoptosis and loss of melanocytes. At the same time these factors have a role in switching-off of the immune responses and cell mediated cytotoxicity.
Keywords
Vitiligo, Fas, FasL, Apoptosis
To cite this article
Fatma Y. Saleh, Sherif Shoukry Awad, Irene M. Sadek, Lymphocytic Expression of Fas and FasL Apoptotic Markers in Vitiligo, Clinical Medicine Research. Vol. 2, No. 5, 2013, pp. 105-109. doi: 10.11648/j.cmr.20130205.13
References
[1]
Spritz RA. Six Decades of Vitiligo Genetics: Genome-Wide Studies Provide Insights into Autoimmune Pathogenesis. J Invest Dermatol. 2011; 132(2): 268-73.
[2]
Oyarbide-Valencia K, van den Boorn JG, Denman CJ, et al.. Therapeutic implications of autoimmune vitiligo T cells. Autoimmun Rev. 2006; 5(7): 486-92.
[3]
van den Boorn JG, Konijnenberg D, Dellemijn TA, et al. Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J Invest Dermatol. 2009; 129(9): 2220-32.
[4]
Steitz J, Wenzel J, Gaffal E and Tuting T. Initiation and regulation of CD8+T cells recognizing melanocytic antigens in the epidermis: implications for the pathophysiology of vitiligo. Eur J Cell Biol. 2004; 83(11): 797-803.
[5]
Wajant H, Pfizenmaier K and Scheurich P. Non-apoptotic Fas signaling. Cytokine Growth Factor Rev. 2003; 14(1): 53-66.
[6]
Wajant H. The Fas signaling pathway: more than a paradigm. Science. 2002; 296(5573): 1635-6.
[7]
Tarzi RM, Sharp PE, McDaid JP, et al. Mice with defective Fas ligand are protected from crescentic glomerulonephritis. Kidney Int. 2011; 81(2): 170-8.
[8]
Li M, Sun D, Li C, et al. Functional polymorphisms of the FAS gene associated with risk of vitiligo in Chinese populations: a case-control analysis. J Invest Dermatol. 2008; 128(12): 2820-4.
[9]
Bing X, Hongyang L, Weimin C, et al. Pigmentary disorders. Journal of Dermatology. 2010; 37 (1): 111–8.
[10]
Zhang QG, Fang CH, Zeng J, et al. The Fas and FasL expression of peripheral blood T lymphocytes in the patients with active vitiligo vulgaris. Journal of Clinical Dermatology. 2006; 03: 147-8.
[11]
Lee AY, Youm YH, Kim NH, et al. Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis. Br J Dermatol. 2004; 151(5): 995-1003.
[12]
Siegel RM, Chan FK, Chun HJ, Lenardo MJ. The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity. Nat. Immunol. 2000; 1: 469-74.
[13]
Paulsen M and Janssen O. Pro- and anti-apoptotic CD95 signaling in T cells. Cell Commun Signal. 2011; 9: 7-14.
[14]
Dianzani U, Chiocchetti A and Ramenghi U. Role of inherited defects decreasing Fas function in autoimmunity. Life Sci. 2003; 72(25): 2803-24.
[15]
Osborn SL, Diehl G, Han SJ, et al. Fas-associated death domain (FADD) is a negative regulator of T-cell receptor-mediated necroptosis. Proc Natl Acad Sci U S A. 2010; 107(29): 13034-9.
[16]
Lambe T, Leung JC, Bouriez-Jones T, et al. CD4 T cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions. J Immunol. 2006; 177(5): 3055-62.
[17]
Montagna P, Brizzolara R, Soldano S, et al. Sex hormones and leflunomide treatment of human macrophage cultures: effects on apoptosis. Int J Clin Exp Med. 2009; 2(3): 221-32.
[18]
Awad SS. Leflunomide is a possible deactivator for vitiligo, a pilot study. J Eur Acad Dermatol Venereol. 2012; 26(9): 1173.
[19]
Mullighan CG, Heatley S, Lester S, et al. Fas gene promoter polymorphisms in primary Sjögren's syndrome. Ann Rheum Dis. 2004; 63:98–101.
[20]
Nolsøe RL, Kelly JA, Pociot F, et al. Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia. Genes Immun. 2005; 6:699–706.
[21]
Kim NH, Jeon S, Lee HJ and Lee AY. Impaired PI3K/Akt activation-mediated NF-kappaB inactivation under elevated TNF-alpha is more vulnerable to apoptosis in vitiliginous keratinocytes. J Invest Dermatol. 2007; 127(11): 2612-7.
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