title: Single-cell dynamics of mast cell-CD4+ CD25+ regulatory T cell interactions.
abstract: The biological behavior of immune cells is determined by their intrinsic properties and interactions with other cell populations within their microenvironment. Several studies have confirmed the existence of tight spatial interactions between mast cells (MCs) and Tregs in different settings. For instance, we have recently identified the functional cross-talk between MCs and Tregs, through the OX40L-OX40 axis, as a new mechanism of reciprocal influence. However, there is scant information regarding the single-cell dynamics of this process. In this study, time-lapse video microscopy revealed direct interactions between Tregs and MCs in both murine and human cell co-cultures, resulting in the inhibition of the MC degranulation response. 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 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.
authors.affiliation: Department of Biomedical Science and Technology, M.A.T.I. Centre of Excellence, University of Udine, Udine, Italy. barbara.frossi@uniud.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Frossi
authors.forename: Federica
authors.initials: F
authors.lastname: D'Incà
authors.forename: Enrico
authors.initials: E
authors.lastname: Crivellato
authors.forename: Riccardo
authors.initials: R
authors.lastname: Sibilano
authors.forename: Giorgia
authors.initials: G
authors.lastname: Gri
authors.forename: Marco
authors.initials: M
authors.lastname: Mongillo
authors.forename: Luca
authors.initials: L
authors.lastname: Danelli
authors.forename: Laura
authors.initials: L
authors.lastname: Maggi
authors.forename: Carlo E
authors.initials: CE
authors.lastname: Pucillo
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D015550:Cell Degranulation; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D008407:Mast Cells / Q000276:immunology* / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D018715:Microscopy, Video; D053278:OX40 Ligand / Q000378:metabolism; D053262:Receptors, OX40 / Q000378:metabolism; D059010:Single-Cell Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D053278:OX40 Ligand; D053262:Receptors, OX40; D002118:Calcium