Controlling Mast Cell Activation and Homeostasis: Work Influenced by Bill Paul That Continues Today

Abstract

Mast cells are tissue resident, innate immune cells with heterogenous phenotypes tuned by cytokines and other microenvironmental stimuli. Playing a protective role in parasitic, bacterial, and viral infections, mast cells are also known for their role in the pathogenesis of allergy, asthma, and autoimmune diseases. Here, we review factors controlling mast cell activation, with a focus on receptor signaling and potential therapies for allergic disease. Specifically, we will discuss our work with FcεRI and FγR signaling, IL-4, IL-10, and TGF-β1 treatment, and Stat5. We conclude with potential therapeutics for allergic disease. Much of these efforts have been influenced by the work of Bill Paul. With many mechanistic targets for mast cell activation and different classes of therapeutics being studied, there is reason to be hopeful for continued clinical progress in this area.

Mast Cell-Mediated Orchestration of the Immune Responses in Human Allergic Asthma: Current Insights

“…MCs express a number of receptors that regulate their activation [82]. Tezepelumab (AMG-157) is a fully human neutralizing IgG2 anti-TSLP monoclonal antibody.…”

The Role of Stem Cell Factor in Hyperpigmented Skin Lesions

“…Prignano et al, (2006) also noticed positive SCF staining but in a minority of metastatic melanoma cases. Additionally, Caslin et al, (2018) suggested that SCF partly causes the increased number of mast cells, which may enhance tumor cell proliferation, leading to tumor progression.…”

Augmentation of Mast Cell Stability, a Therapeutic Strategy for Idiopathic Pulmonary Fibrosis

“…Mast cells commonly become activated through conjugation of IgE with FcεRI receptors, which are present in excess on the mast cell surface [43] . Activation of mast cell can also occur by means of cytokines and other micro-environmental stimuli [44] . Generally, mast cells release various kinds of vasoactive and inflammatory mediators stored in granules within cytoplasm after receiving activation threshold [45] where, intracellular calcium ion concentration plays a significant role in the degranulation process [46] .…”

“…Chronic inflammation as an important underlying mechanism of IPF [10] , mast cell degranulation materializes frequently and creates imbalance between profibrotic and antifibrotic mediators [16] . These conditions lead to continuous disturbance in homeostasis [44] . In chronic inflammatory condition, degranulation of mast cells may take place in uncontrolled manner and releases excess of profibrotic mediators (cytokines, chemokines, growth factors and proteases) within target organ as represented in fig.…”