Date of Graduation

8-2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Cell & Molecular Biology (PhD)

Degree Level

Graduate

Department

Cell & Molecular Biology

Advisor/Mentor

Erf, Gisela F.

Committee Member

Du, Yuchun

Second Committee Member

McNabb, David S.

Third Committee Member

Thallapuranam, Suresh

Keywords

Animal model; Autoimmunity; Immunology; Smyth chicken; Translational immunology; Vitiligo

Abstract

Vitiligo is an acquired de-pigmentation disorder characterized by the post-natal loss of epidermal melanocytes (pigment-producing cells) resulting in the appearance of white patches in the skin. The Smyth line of chicken is the only model for vitiligo that shares all the characteristics of the human condition including: spontaneous post-natal loss of melanocytes, interactions between genetic, environmental and immunological factors and associations with other autoimmune diseases. In addition, an avian model for vitiligo has the added benefit of an easily accessible target tissue (a growing feather) that allows for the repeated sampling of an individual and thus the continuous monitoring of local immune responses over time. Here, we sought to gain a comprehensive understanding of the initiating events leading to expression of vitiligo in growing feathers by monitoring the infiltration of leukocytes and concurrent immunological activities beginning prior-to visual onset and continuing throughout disease development. Furthermore, we examined the nature of the melanocyte-specific recall (i.e. memory) response by re-introducing the target cell (melanocyte) into the target tissue (growing feather) of completely depigmented Smyth chickens via intradermal injection. Lastly, we sought to gain insights into the role of melanocytes in provoking the autoimmune response by measuring the expression of co-stimulatory molecules in the presence of oxidative stress-inducing H2O2. During the primary response we observed characteristic rises in infiltrating B and αβ T cells as well as evidence of active recruitment and cell-mediated immune activities leading up to visual onset. Examination of growing feathers from vitiligo-susceptible Brown line chickens revealed novel anti-inflammatory immune activities which may be responsible for preventing vitiligo. We also observed characteristic memory-like increases in B and T cells as well as increases in recruitment and cell-mediated immune activities in response to injection of melanocytes into growing feathers of completely depigmented Smyth chickens. Lastly, we observed increased expression of CD40 and B7-1 in melanocytes derived from growing feathers of Smyth chickens treated with H2O2. Collectively, these results further support the notion of cell-mediated immune destruction of melanocytes in growing feathers. Furthermore, these data open new avenues of study in the vitiligo-prone Smyth line and vitiligo-susceptible Brown line chickens.

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