Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

• Published in: British journal of dermatology (1951) Vol. 181; no. 4; pp. 677 - 690
• Main Authors: Clayton, R.W., Göbel, K., Niessen, C.M., Paus, R., Steensel, M.A.M., Lim, X.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-10-2019
• Subjects: Acne; Acne Vulgaris - immunology; Acne Vulgaris - pathology; Androgens; Animal models; Animals; Cell differentiation; Cell Differentiation - genetics; Cell Differentiation - immunology; Comedones; Cysts; Disease Models, Animal; ErbB protein; Fibroblast growth factor receptor 2; Growth factors; Homeostasis; Humans; Insulin; Lipids; Menopause; Mice; Mice, Transgenic; Molecular modelling; Paracrine signalling; Pathogenesis; Progenitor cells; Retinoids; Sebaceous gland; Sebaceous Glands - immunology; Sebaceous Glands - metabolism; Sebaceous Glands - pathology; Sebum - metabolism; Signal transduction; Stem cells; Therapeutic targets; Transcription factors; Tyrosine; Wnt protein; Wnt Signaling Pathway - genetics; Wnt Signaling Pathway - immunology
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.17981

Summary
Background
Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo‐associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the ‘comedo switch’. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG‐associated skin disorders.
Results
In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and insulin/insulin‐like growth factor 1 receptors; peroxisome proliferator‐activated receptor γ; aryl hydrocarbon receptor; and the Wnt signalling pathway. Where possible, the cellular and molecular mechanisms by which these regulatory factors control SG biology are indicated, along with considerations as to how they might contribute to acne pathogenesis.
Conclusions
Future research should seek to establish the relative importance, and causative relationships, of altered sebum production, sebum composition, inflammation and abnormal differentiation of sebaceous progenitors to the process of comedo formation in acne. Such an understanding will allow for therapeutic targeting of regulatory factors that control SG homeostasis, with the aim of treating acne.
What's already known about this topic?
Sebaceous glands (SGs) are skin appendages that synthesize lipids (sebum).
Several skin diseases, including acne, feature abnormal SGs.
Androgens are essential for both SG maintenance and acne.
Retinoids and oestrogens, which can be used to treat acne effectively, cause dramatic SG involution.
What does this study add?
We synthesize both historical and current literature and generate testable hypotheses regarding SG homeostasis and acne pathogenesis.
We present an up‐to‐date model of the cellular and molecular mechanisms that underpin SG homeostasis.
We discuss evidence supporting a model of comedo formation where the progenitor cells that contribute to the SG and infundibulum differentiate abnormally.
Linked Editorial: Van Steensel. Br J Dermatol 2019; 181:647–648.