Citation: Wo ´ zniak, E.; Owczarczyk-Saczonek, A.; Lange, M.; Czarny, J.; Wygonowska, E.; Placek, W.; Nedoszytko, B. The Role of Mast Cells in the Induction and Maintenance of Inflammation in Selected Skin Diseases. Int. J. Mol. Sci. 2023, 24, 7021. https://doi.org/ 10.3390/ijms24087021 Academic Editor: Christopher Jackson Received: 28 February 2023 Revised: 23 March 2023 Accepted: 7 April 2023 Published: 10 April 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). International Journal of Molecular Sciences Review The Role of Mast Cells in the Induction and Maintenance of Inflammation in Selected Skin Diseases Ewelina Wo´ zniak 1 , Agnieszka Owczarczyk-Saczonek 1 , Magdalena Lange 2 , Justyna Czarny 2 , Ewa Wygonowska 1 , Waldemar Placek 1 and Boguslaw Nedoszytko 2,3, * 1 Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, The University of Warmia and Mazury, 10-229 Olsztyn, Poland 2 Departmentof Dermatology, Venereology and Allergology, Medical University of Gdansk, 80-214 Gdansk, Poland 3 Invicta Fertility and Reproductive Centre, Molecular Laboratory, 81-740 Sopot, Poland * Correspondence: bned@gumed.edu.pl Abstract: Under physiological conditions, skin mast cells play an important role as guardians that quickly react to stimuli that disturb homeostasis. These cells efficiently support, fight infection, and heal the injured tissue. The substances secreted by mast cells allow for communication inside the body, including the immune, nervous, and blood systems. Pathologically non-cancerous mast cells participate in allergic processes but also may promote the development of autoinflammatory or neoplastic disease. In this article, we review the current literature regarding the role of mast cells in autoinflammatory, allergic, neoplastic skin disease, as well as the importance of these cells in systemic diseases with a pronounced course with skin symptoms. Keywords: mast cell activation; urticaria; Kounis syndrome; Ehlers–Danlos syndrome; pseudoallergy; red man syndrome; psoriasis; rosacea; atopic dermatitis; allergic contact dermatitis; cutaneous mastocytosis; mast cell activation syndrome 1. Introduction Mast cells (MCs) are mononuclear cells originating from pluripotential hematopoietic cells in the bone marrow. MCs are derived from the myeloid lineage as granulocytes, monocytes, erythrocytes, and megakaryocytes [1]. Progenitors with mast-cell-forming potential are defined as CD34+, KIT+, FcεRI + cells [2]. According to some authors, the integrin α4β7 mediates the migration of MC progenitors to peripheral tissues, where they finally differentiate into mature cells [3]. The mastocyte progenitor cell transforms into a mature MC ultimately in the peripheral tissue under the influence of various factors of a specific microenvironment. The diversification, growth, and maturing of MCs in tissues may take between several days and up to even several weeks [4]. MCs can be divided into two groups, depending on the secreted granularity: MCs(T)—MCs releasing only tryptase—and MCs(TC)—MCs secreting, in addition to tryptase, chymase, caboxypeptidase, and a cathepsin G-like proteinase. MCs(T) are founded in the mucous membranes of the respiratory system and the digestive tract, that is, in places inside of the body where MCs come into contact with factors from the outside world (e.g., food, pollen, drugs, microorganisms). However, MCs(TC) localize in the submucosa and connective tissue adjacent to the conjunctiva and skin [5,6]. Due to the strategic location of MCs in tissues adjacent to the external environment, they physiologically play a role in the processes of innate and acquired immunity against microbes, as well as stimulate tissue healing after trauma. Moreover, MCs are involved in the pathogenesis of many allergic, autoinflammatory, and cancer diseases [7]. MCs express a lot of different membrane receptors and molecules, and are capable of producing a wide range of mediators, cytokines, and chemokines, with pro- or anti- inflammatory effects. Int. J. Mol. Sci. 2023, 24, 7021. https://doi.org/10.3390/ijms24087021 https://www.mdpi.com/journal/ijms