Immune-mediated alopecias and their mechanobiological aspects

Abstract

Alopecia is a non-specific term for hair loss clinically diagnosed by the hair loss pattern and histological analysis of patient scalp biopsies. The immune-mediated alopecia subtypes, including alopecia areata, lichen planopilaris, frontal fibrosing alopecia, and central centrifugal cicatricial alopecia, are common, significant forms of alopecia subtypes. For example, alopecia areata is the most common autoimmune disease with a lifetime incidence of approximately 2% of the world's population. In this perspective, we discuss major results from studies of immune-mediated alopecia subtypes. These studies suggest the key event in disease onset as the collapse in immune privilege, which alters the hair follicle microenvironment, e.g., upregulation of major histocompatibility complex molecules and increase of cytokine production, and results in immune cell infiltration, inflammatory responses, and damage of hair follicles. We note that previous studies have established that the hair follicle has a complex mechanical microenvironment, which may regulate the function of not only tissue cells but also immune cell infiltrates. This suggests a potential for mechanobiology to contribute to alopecia research by adding new methods, new approaches, and new ways of thinking, which is missing in the existing literature. To fill this a gap in the alopecia research space, we develop a mechanobiological hypothesis that alterations in the hair follicle microenvironment, specifically in the mechanically responsive tissues and cells, partially due to loss of immune privilege, may be contributors to disease pathology. We further focus our discussion on the potential for applying mechanoimmunology to the study of T cell infiltrates in the hair follicle, as they are considered primary contributors to alopecia pathology. To establish the connection between the mechanoimmunological hypothesis and immune-mediated alopecia subtypes, we discuss what is known about the role of T cells in immune-mediated alopecia subtypes, using the most extensively studied AA as our model.

Keywords: Alopecia; Autoimmunity; Hair loss; Mechanobiology; Mechanoimmunology.