All ETDs from UAB

Advisory Committee Chair

Melissa L Harris

Advisory Committee Members

Asim Bej

Vithal K Ghanta

Document Type

Thesis

Date of Award

2021

Degree Name by School

Master of Science (MS) College of Arts and Sciences

Abstract

Anecdotally, humans can experience loss of hair color or hair graying after infection or vaccination yet our understanding of how melanocyte biology and the innate immune system interact is incomplete. Mouse models of hair graying have been used to reveal numerous mechanisms that adversely affect the melanocyte system within the hair follicle, and one such mouse model highlights a molecular link between the transcription factor SOX10, melanogenesis and innate immune dysregulation. SOX10 is a transcription factor critical for neural crest development and melanogenesis, and when overexpressed in the Tg(Dct-Sox10)CF1-10 mouse line causes a sensitivity to viral mimic Poly(I:C) that results in loss of melanocyte stem cells and subsequent hair graying. Based on RNA-Seq data, these Tg(Dct-Sox10)CF1-10 mice upregulate multiple interferon stimulated genes within the skin, suggesting a relationship between SOX10 expression and innate immune gene regulation. By utilizing in vivo and in vitro systems combined with gene expression analysis by RT-qPCR, we were able to observe parts of the complex interactions between the innate immune system, melanogenesis, and the melanocyte. Alternate Tg(Dct-Sox10) founder lines suggest that innate immune upregulation resulted from the dramatic increase in SOX10 expression from the CF1-10 line, creating a line specific effect. RT-qPCR analysis of Tg(Dct-Sox10) mice lacking melanogenesis showed a cursory link iii between melanin synthesis and innate immune upregulation. Finally, cellular transfections using the pDct-mSox10-Mp1 plasmid demonstrated a more direct regulatory relationship between SOX10 expression and the expression of at least one type of interferon. Overall, our results demonstrate interactions between increasing SOX10 expression, excess melanogenesis, and the dysregulation of the innate immune system. Through our increasing understanding of these interactions we can more easily identify previously unknown factors leading to the loss of melanocytes due to innate immune dysregulation, and how melanocyte loss might change due to other influences such as infection or aging.

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