Mast cells or “Mastzellen” were first described by Paul Ehrlich in his 1878 thesis. The metachromatic cells were shown to be concentrated around blood vessels, nerves, and glandular ducts as well as inflammatory and neoplastic foci. The cells originate from hematopoietic stem cells in the bone marrow. Because of their importance in allergen/IgE-mediated allergic reactions, most of the studies on mast cells have traditionally focused on their role in allergy. However, the last fifteen years have witnessed the changing tide and this field has provided convincing evidence that these cells are an important physiological player in innate immunity, adaptive immunity, and immune tolerance. Mast cells can be activated by an invaded pathogen, control the migration of antigen-presenting dendritic cells or work themselves as antigen-presenting cells, thus contribute to the initiation of innate immune and adaptive immune reactions. On the other hand, mast cells recruited under certain conditions are essential for successful organ transplantion, thus crucial for immune tolerance. In addition to immediate hypersensitivity and host defense against certain parasites and bacteria, a better understanding of mast cells’ role in airway inflammation or asthma was recently furnished. We have also seen a great progress in their pathogenic role in autoimmune diseases including experimental allergic encephalomyelopathy (EAE) and rheumatoid arthritis. Furthermore, recent studies suggest that mast cells participate in atherosclerosis and obesity.
Mast cell progenitors that have left the bone marrow enter the circulation and quickly migrate to tissues. They mature in situ under the influence of the local cytokine milieu. We have seen some progress in the migratory process leading to mature mast cells. These mast cells are exposed to cytokines, growth factors, antigens, and pathogens. Progress in this area is illustrated by our dizzily complex signaling pathways evoked by IL-3, stem cell factor, and IgE plus antigen. Fc?RI (high-affinity IgE receptor)-mediated signal transduction is one of the most well-characterized receptor systems. Fc?RI activation induced with IgE and antigen results in the release of substances preloaded in secretory granules as well as de novo synthesized lipids and polypeptides, which lead to allergic reactions. Positive signals must be antagonized by negative signals to make sure that activation of the cells do not go unchecked and is followed by timely ceasing of activation. Accumulating evidence indicates that mast cells are armed with many more activating and negative regulatory innate receptors. It will be important to complete the list of these receptors and to understand their unique functions as well as their relative contributions to the biology of mast cells. A new, but less certain, frontier of research is on mast cells’ interactions with other cells such as T cells and eosinophils or exosomes. Accumulation of transformed mast cells, i.e., mastocytosis, has been increasingly well understood. Equally interesting, the complex role of mast cells in tumorigenesis has begun to be deciphered.
The rich information brought by the Human and Mouse Genome Projects, along with technological progresses in genomics, proteomics, and epigenetics, has begun to be applied to mast cell research. We hope that the review articles in this Hot Topic issue will serve as the one-stop resource of mast cell biology for new and established researchers alike.
Mast cells or “Mastzellen” were first described by Paul Ehrlich in his 1878 thesis. The metachromatic cells were shown to be concentrated around blood vessels, nerves, and glandular ducts as well as inflammatory and neoplastic foci. The cells originate from hematopoietic stem cells in the bone marrow. Because of their importance in allergen/IgE-mediated allergic reactions, most of the studies on mast cells have traditionally focused on their role in allergy. However, the last fifteen years have witnessed the changing tide and this field has provided convincing evidence that these cells are an important physiological player in innate immunity, adaptive immunity, and immune tolerance. Mast cells can be activated by an invaded pathogen, control the migration of antigen-presenting dendritic cells or work themselves as antigen-presenting cells, thus contribute to the initiation of innate immune and adaptive immune reactions. On the other hand, mast cells recruited under certain conditions are essential for successful organ transplantion, thus crucial for immune tolerance. In addition to immediate hypersensitivity and host defense against certain parasites and bacteria, a better understanding of mast cells’ role in airway inflammation or asthma was recently furnished. We have also seen a great progress in their pathogenic role in autoimmune diseases including experimental allergic encephalomyelopathy (EAE) and rheumatoid arthritis. Furthermore, recent studies suggest that mast cells participate in atherosclerosis and obesity.
Mast cell progenitors that have left the bone marrow enter the circulation and quickly migrate to tissues. They mature in situ under the influence of the local cytokine milieu. We have seen some progress in the migratory process leading to mature mast cells. These mast cells are exposed to cytokines, growth factors, antigens, and pathogens. Progress in this area is illustrated by our dizzily complex signaling pathways evoked by IL-3, stem cell factor, and IgE plus antigen. Fc?RI (high-affinity IgE receptor)-mediated signal transduction is one of the most well-characterized receptor systems. Fc?RI activation induced with IgE and antigen results in the release of substances preloaded in secretory granules as well as de novo synthesized lipids and polypeptides, which lead to allergic reactions. Positive signals must be antagonized by negative signals to make sure that activation of the cells do not go unchecked and is followed by timely ceasing of activation. Accumulating evidence indicates that mast cells are armed with many more activating and negative regulatory innate receptors. It will be important to complete the list of these receptors and to understand their unique functions as well as their relative contributions to the biology of mast cells. A new, but less certain, frontier of research is on mast cells’ interactions with other cells such as T cells and eosinophils or exosomes. Accumulation of transformed mast cells, i.e., mastocytosis, has been increasingly well understood. Equally interesting, the complex role of mast cells in tumorigenesis has begun to be deciphered.
The rich information brought by the Human and Mouse Genome Projects, along with technological progresses in genomics, proteomics, and epigenetics, has begun to be applied to mast cell research. We hope that the review articles in this Hot Topic issue will serve as the one-stop resource of mast cell biology for new and established researchers alike.
