Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich's visions to precision medicine concepts

Abstract

The origin and functions of mast cells (MCs) have been debated since their description by Paul Ehrlich in 1879. MCs have long been considered 'reactive bystanders' and 'amplifiers' in inflammatory processes, allergic reactions, and host responses to infectious diseases. However, knowledge about the origin, phenotypes and functions of MCs has increased substantially over the past 50 years. MCs are now known to be derived from multipotent hematopoietic progenitors, which, through a process of differentiation and maturation, form a unique hematopoietic lineage residing in multiple organs. In particular, MCs are distinguishable from basophils and other hematopoietic cells by their unique phenotype, origin(s), and spectrum of functions, both in innate and adaptive immune responses and in other settings. The concept of a unique MC lineage is further supported by the development of a distinct group of neoplasms, collectively referred to as mastocytosis, in which MC precursors expand as clonal cells. The clinical consequences of the expansion and/or activation of MCs are best established in mastocytosis and in allergic inflammation. However, MCs have also been implicated as important participants in a number of additional pathologic conditions and physiological processes. In this article, we review concepts regarding MC development, factors controlling MC expansion and activation, and some of the fundamental roles MCs may play in both health and disease. We also discuss new concepts for suppressing MC expansion and/or activation using molecularly-targeted drugs.

IgE and IgG Antibodies as Regulators of Mast Cell and Basophil Functions in Food Allergy

“…Mast cells are long-lived tissue resident cells that differentiate locally from bloodborne progenitors (35). They are often found in vascularized sites that are exposed to the external environment and microbiome, such as the mucosa of the gastrointestinal and respiratory tracts (36). Basophils are short-lived cells that mature in the bone marrow, enter the circulation and can either be activated intravascularly or traffic to sites of inflammation to exert their functions (37)(38)(39).…”

“…Because of their anatomic localization in barrier tissues, mast cells are likely to be one of the first cell types to encounter and respond to pathogens, making them important effector cells of the innate immune response. Several groups have identified their protective roles in bacterial infection and they are also critical in the immune response to parasites (36,40). They express pathogen recognition receptors and can release anti-microbial peptides upon activation.…”

Harnessing the Power of Mast Cells in unconventional Immunotherapy Strategies and Vaccine Adjuvants

“…Mast cells originate from the bone marrow and circulate as immature progenitors in the blood until finally maturing in the tissue in which they reside for the remainder of their life [ 7 ]. Some evidence suggests that mast cells instead mostly originate from local progenitor cell pools initially established by successive waves of colonization that occur during embryogenesis [ 8 , 9 , 10 , 11 ]. While mast cells derived from earlier waves tend to be replaced by mast cells from later waves, the kinetics of these changes vary by tissue [ 10 ].…”

“…Mature human mast cells are generally divided into two different subpopulations based on their protease content: those with tryptase (MC T ) equivalent to mucosal mast cells in mice, and those with both tryptase and chymase (MC CT ) equivalent to connective tissue mast cells in mice [ 13 ]. Mast cell heterogeneity extends beyond this binary division, though, and mast cells can express different receptors, proteases and responses to external stimuli based on the stage of development and signals from their surrounding microenvironment [ 8 ]. Though not discussed in this review, it is important to keep in mind that mast cell phenotype can vary significantly, potentially limiting the applicability of treatments discussed below to situations other than those assessed in a given study.…”

“…The mouse orthologue of MRGPRX2, MrgprB2, differs in its sensitivity to various stimuli [ 32 ]. Human mast cells also respond differently to cytokines and growth factors as compared to mouse cells and their mouse orthologues, requiring different subsets for proliferation and maturation [ 8 ]. Finally, mast cells can also express different receptors on their surface depending on the tissue they are isolated from [ 8 ].…”