Involvement of Different Genes Expressions during Immunological and Inflammatory Responses in Vitiligo

Abstract

Vitiligo is a condition of the skin distinguished by hypo-pigmentation. Etiology of this disorder is unknown, and several theories and mechanisms have been hypothesized. The inflammatory response in vitiligo is thought to be mediated by polymorphism in genes such as FOXP3, ACE, APE, GSTP1, TLR, SOD, CTLA-4, TAP/LMP gene cluster, etc. Theories including reactive oxygen species model, Nrf2-antioxidant response element (ARE) pathway, WNT pathway, tyrosinase activity, biochemical, molecular, and cellular alterations have been hypothesized to explain vitiligo pathogenesis. Melanosomal proteins are involved in antigen processing. The antigens are expressed to the T-cells in the form of peptides with HLA class II molecules. T-cells are activated in response to the discharge of co-stimulatory molecules such as LFA-3 as well as ICAM-1. An adaptive immune response is thus elicited, and the melanocytes eventually die or start malfunctioning and the skin undergoes hypo-pigmentation. IFN-γ is known to be a melanocyte inhibitor of paracrine origin; it is clearly involved in the early onset of symptoms of vitiligo disease. The surge in the IFN-γ levels mediates augmented expression of ICAM-1 molecule on the melanocytes, thereby establishing cytokine-mediated destruction of melanocytes. Mainly, mediators released by melanocytes and the functionality of keratinocytes decrease the disease activity. Such mediators include ET-1 as well as SCF, increase the pigmentation particularly when a patient is given with the UVB treatment. By scavenging ROS and screening UV radiation, melanin limits the damage caused to the cutaneous cells by UV radiation. Various immune responses play important roles in vitiligo.

Quantitative Outcome Assessment of Color Match and the Extent of Repigmentation after Pixel Array Epidermal Grafting for Head and Neck Stable Vitiligo: A Prospective Cohort Study

“…We postulated that, in addition to retrograde migration of melanocytes from the repigmented epidermis to the leukotrichia area [22], growth factors and cytokines from the micrografts stimulated the hibernating melanocyte stem cells (MSCs). This effect could be particularly accentuated when phototherapy was given [23,24]. MSCs were more deeply located in the scalp and beard area than in the eyebrows [22], corresponding to patient 10 whose skin repigmentation over the submandibular area was 79.9%, but no repigmentation occurred over the white beard by POM 6 (Fig.…”

The Role of NKG2D in Vitiligo

“…While its role as an apoptotic mediator has been shown in multiple cell types (129), in vitiligo, TNF-α inhibits melanogenesis by activating the transcription factor NF-κB (130). In addition, it induces the expression of ICAM-1 on melanocytes (131), allowing for the attachment of T cells and triggering cytotoxicity (132). Moreover, TNF-α inhibits tyrosinase and Trp1 activity, both essential for melanin synthesis (61).…”

Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk

“…45 The apparent non-significant associations of CTLA4 gene expression and variants with the disease phenotype, activity, and severity could indicate that the major role this gene plays is in disease etiology and pathogenesis rather than progression. 46 Collectively, the above findings could support the role of CTLA4 rs231775 played in vitiligo pathogenesis to be related, in part, to…”