Immunobiology: Receptors and signaling in mast cells. Implications in pathology. PI: Margarita Martín Andorrà
Mast cells are immune cells with a recognized function in parasitic and bacterial infections and venom resistance. Due to their location throughout the body, the expression of a broad spectrum of receptors, and the ability to respond very quickly by releasing preformed inflammatory mediators stored in their granules, mast cells regulate many physiological processes. In terms of pathology, they are the main effector cells in allergic inflammatory reactions and are involved in chronic inflammatory disorders, autoimmune disorders, and cancer, among others. Our group is interested in characterizing mast cell receptors and their signaling concerning pathology. We are a basic research group collaborating with clinical groups. https://www.clinicbarcelona.org/idibaps/areas-y-programas/biopatologia-y-bioingenieria-respiratoria-cardiovascular-y-renal/inmunoalergia-respiratoria-clinica-y-experimental-irce.
The classic and most studied pathway of mast cell activation begins with the binding of IgE to the high-affinity receptor for IgE (FcepsilonRI) and the subsequent release of histamine and other mediators after exposure to the allergen. We have identified a mutation in KARS. This gene encodes Lysyl-tRNA synthetase, and the mutation constitutively activates the microphthalmia-associated transcription factor (MITF), responsible for histamine synthesis and the severity of allergic reactions resulting in anaphylaxis.
The KIT receptor is expressed on progenitor cells in the bone marrow that give rise to myeloid and lymphoid lines. It is found only in mast cells after immune cell differentiation. KIT is a tyrosine kinase receptor involved in cell survival and proliferation. Receptor deregulations are associated with mastocytosis, gastrointestinal stromal tumors (GIST), and other oncological pathologies. Our research has shown that MITF inhibition reduces mast cell viability and proliferation in a mastocytosis model and also inhibits tumor proliferation in vitro and in vivo GIST models (human cell lines and xenograft experiments).
The MRGPRX2 receptor, with seven transmembrane domains associated with G protein, is expressed in mast cells and neurons, playing a role in skin immunity and pain. It is responsible for adverse reactions that can lead to anaphylaxis to various drugs. Studies by our group have shown that MRGPRX2 responds to anesthetic and analgesic drugs. MRGPRX2 is also associated with inflammatory processes such as chronic urticaria and atopic dermatitis.
The appropriate activation and adjustment of mast cell responses are conditioned by a complex set of factors (adapter molecules, kinases, phosphatases, transcription factors, coreceptors), and the deregulation of these molecules can contribute to pathologies associated with these cells. Characterizing these factors can aid in diagnosis and may represent therapeutic targets.
KEYWORDS: Mast cell receptors, Signal transduction, Innate immunity, Mast cell-related disorders, KIT oncogenic diseases
Margarita Martín-Andorrà
PhD
martin_andorra@ub.edu
Berenice Carrillo Rodriguez
TFM student. Master in Translational Medicine
bcarriro43@alumnes.ub.edu
Mario Guerrero Grueso
Technician
mguerrero@ub.edu
Laia Ollé Boix
Predoctoral researcher
lolle@ub.edu
Lihong Song
Predoctoral researcher
lihongsong@ub.edu
Maria Tsirakmani
Erasmus student
maria.n.tsirakmani@gmail.com
Diego Urdiales Santidrián
TFM student. Advanced Immunology Master
durdiasa7@alumnes.ub.edu
