The Vitamin-A-metabolite retinoic acid (RA) acts as a master regulator of cellular programs. Mast cells (MCs) are primary effector cells of type-I-allergic reactions. We recently uncovered that human cutaneous MCs are enriched with RA network components over other skin cells. Yet, direct experimental evidence on the significance of the RA-MC axis is limited. Here, skin-derived cultured MCs were...

To investigate why responses of mast cells to antigen-induced IgE receptor (FcεRI) aggregation depend nonlinearly on antigen dose, we characterized a new artificial ligand, DF3, through complementary modeling and experimentation. This ligand is a stable trimer of peptides derived from bacteriophage T4 fibritin, each conjugated to a hapten (DNP). We found low and high doses of DF3 at which degra...

Mast cells (MCs) are key effector cells of IgE-FcεRI- or MrgprX2-mediated signaling event. Shuang-Huang-Lian (SHL), a herbal formula from Chinese Pharmacopoeia, has been clinically used in type I hypersensitivity. Our previous study demonstrated that SHL exerted a non-negligible effect on MC stabilization. Herein, we sought to elucidate the molecular mechanisms of the prominent anti-allergic ab...

Mast cells (MC) are key mediators of the immune system, most prominently known for their role in eliciting harmful allergic reactions. Mast cell mediator release (e.g. by degranulation) is triggered by FcεRI recognition of antigen - IgE complexes. Until today no therapeutic targeting of this and other mast cell activation pathways is established. Among possible new candidates there are tetraspa...

Sphingolipid metabolites are emerging as important signaling molecules in allergic diseases specifically asthma. One of the sphingolipid metabolite, sphingosine-1-phosphate (S1P), is involved in cell differentiation, proliferation, survival, migration, and angiogenesis. In the allergic diseases, alteration of S1P levels influences the differentiation and responsiveness of mast cells (MCs). S1P ...

Mast cells play a key role in the induction of anaphylaxis, a life-threatening IgE-dependent allergic reaction, by secreting chemical mediators that are stored in secretory granules. Degranulation of mast cells is triggered by aggregation of the high-affinity IgE receptor, FcεRI, and involves dynamic rearrangement of microtubules. Although much is known about proximal signals downstream of FcεR...

TRPM4 proteins form Ca(2+)-activated non selective cation (CAN) channels that affect transmembrane Ca(2+)-influx by determining the membrane potential. Tight control of the intracellular Ca(2+) concentration is essential for mast cell responses. In this study, we analyzed the expression of TRPM4 in peritoneal mast cells (PCMC) as a model for connective tissue type mast cells with respect to Fcε...

Mast cells, activated by Ag via FcεRI, release an array of proinflammatory mediators that contribute to allergic disorders, such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation, and survival, and under acute conditions, it enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fata...

Davallia mariesii Moore (Drynaria rhizome extract (DRE)) is widely known for its efficacy in treating inflammation, arteriosclerosis, and bone injuries. This study evaluated whether treatment with DRE inhibited FcɛRI-mediated allergic responses in the RBL-2H3 mast cells and investigated the early- and late-phase mechanisms by which DRE exerts its antiallergic effects. IgE anti-DNP/DNP-HSA-sensi...

Chronic idiopathic/spontaneous urticaria (CIU/CSU), which affects ~1% of the United States population, is defined as recurrent hives for >6 weeks (Kaplan and Greaves, 2009). Active CIU/CSU patients uniquely display suppressed basophil FcεRI-mediated histamine release (BHR) (Saini, 2014). This is a feature that improves in disease remission (Eckman et al., 2008; Kern and Lichtenstein, 1976; Oliv...