MCs incubated with WT, but not OX40-deficient, Tregs mediated numerous and long-lasting interactions and displayed different morphological features lacking the classical signs of exocytosis.

MC degranulation and Ca2+ mobilization upon activation were inhibited by Tregs on a single-cell Selumetinib mw basis, without affecting overall cytokine secretion. Transmission electron microscopy showed ultrastructural evidence of vesicle-mediated secretion reconcilable with the morphological pattern of piecemeal degranulation. Our results suggest that MC morphological and functional changes following MC–Treg interactions can be ascribed to cell–cell contact and represent a transversal, non-species-specific mechanism of immune response regulation. Further research, looking at the molecular composition of this interaction will broaden our understanding of its contribution to immunity. In past decades, it has become widely accepted that the contribution of mast cells (MCs) to immunity goes far beyond their well-known role in allergy. Several lines of evidence highlight an emerging GDC-0449 order role

for MCs in numerous stages of both the innate and adaptive immune responses by direct communication with other immune cells 1. Functional interplay between MCs and B cells 2, MCs and both effector T cells 3 and Tregs 4, 5 or MCs and eosinophils 6, 7 have been suggested by studies documenting Rebamipide their co-localization not only in peripheral tissue, but also in lymphatic organs during acquired immune responses, including those involved in host defense, autoimmunity and allergic disorders 2, 5. These cell–cell interactions have been shown to be bi-directional, fulfilling mutually regulatory and/or modulatory roles, including influences on cellular processes such as growth, proliferation, activation, migration and Ag presentation 2–5. Beyond the paracrine communication exerted by cytokines, MCs express a wide array of surface molecules that can potentially mediate this cross-talk directly. Recent findings provide mechanistic insight

in support of such observations. It has been reported that MHC class II expression by MCs is strongly induced by Notch signaling and supports effector and regulatory T cell activation 8. MC-mediated Ag presentation also regulates CD8+ T cell proliferation and cell activation 9. Moreover, several classes of co-stimulatory pathways have been identified and characterized for MCs, each able to operate in a specific physiological condition or disease ensuring a highly regulated response 10, 11. It has been shown that direct contact between MCs and effector T cells causes an increase in MC degranulation following high-affinity receptor for IgE (FcεRI) triggering, and a boost of T cell proliferation 12, 13.