Network at a glance: looking at Mast Cells’ range of contact modes

Over the past decades, a new picture of the function of MCs is gradually emerging; these cells have currently gained recognition as true immune effector cells in a variety of settings during innate and adaptive immune responses, but have also the potential to modulate many aspects of immune cells. Besides paracrine communication, it is now clear that the onset and the regulation of a specific immune response is highly complex and requires immune cells to be specially adapted to interact directly with other cells. Such communication can result in different modes of interaction (with respect to morphology and duration) and leads to different outcome. The type and amount of information that is exchanged is determined by the duration of interaction, physical dynamics, identity of receptors and signaling molecules that are engage. Moreover they rely on signals that are transmitted, depending on the activation state of both the cell types, as well as the type of the environment in which the interaction takes place. As MCs are traditionally thought of as a secretory cell type, an intriguing and not yet fully clarified aspect of MC biology concerns their physical interaction with other cellular partners. This work aims to shed light on MC range of contact modes, starting to define a molecular code, in which the differences in timing, spacing and molecular composition of the signaling platform determine the outcome of “MAST CELLular interactions”. Distinct aspects of the interactions with different immune cells have been addressed. Firstly the morphological features and functional profile of MC-regulatory T cell (Treg) synapses have been extensively described: it has been demonstrated that this cross-talk is regulated on a single cell level also providing the first morphological evidence for a role of the OX40-OX40L axis in Treg inhibition of MC function. A more detailed analysis obtained with electron microscopy indicated that MCs interacting with Treg probably underwent selective mediator secretion throughout piecemeal degranulation (PMD). Few additional information were given on the ability of MCs to collect and add up signals to dictate their stringency of binding to Treg cells. Moreover, to explain the inhibitory mechanism exerted by Tregs on MC FceRI-dependent extracellular calcium (Ca2+) flux, the possibility that STIM1 may function as a switch governing in the fate of Ca2+ flux in BMMCs interacting with Tregs was explored. Secondly, an overview of the regulation of MC-B cell adhesiveness under different stimulation conditions was provided. The capacity of naïve B cells and LPS- or CD40-stimulated B lymphocytes to form stable conjugate with MCs was assessed in the absence or in the presence of antigen stimulation, also demonstrating a role of CD40-CD40L axis in the dynamics and functional outcome of this interaction. Finally, a fresh picture of the functional dynamics of MC-Neutrophil interactions has been drawn, showing the existence of a direct cell-contact communication leading to an endocytic process likely corresponding to phagocytosis.