title: CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.
abstract: T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the FcvarepsilonRI-dependent MC degranulation through cell-cell contact involving OX40-OX40L interactions between Treg cells and MCs, respectively. When activated in the presence of Treg cells, MCs showed increased cyclic adenosine monophosphate (cAMP) concentrations and reduced Ca(2+) influx, independently of phospholipase C (PLC)-gamma2 or Ca(2+) release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effects of Treg cells, restoring normal Ca(2+) responses and degranulation. Importantly, the in vivo depletion or inactivation of Treg cells caused enhancement of the anaphylactic response. The demonstrated crosstalk between Treg cells and MCs defines a previously unrecognized mechanism controlling MC degranulation. Loss of this interaction may contribute to the severity of allergic responses.
authors.affiliation: Department of Biomedical Science and Technology, University of Udine, 33100 Udine, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Gri
authors.forename: Silvia
authors.initials: S
authors.lastname: Piconese
authors.forename: Barbara
authors.initials: B
authors.lastname: Frossi
authors.forename: Vanessa
authors.initials: V
authors.lastname: Manfroi
authors.forename: Sonia
authors.initials: S
authors.lastname: Merluzzi
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Antonella
authors.initials: A
authors.lastname: Viola
authors.forename: Sandra
authors.initials: S
authors.lastname: Odom
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
authors.forename: Mario P
authors.initials: MP
authors.lastname: Colombo
authors.forename: Carlo E
authors.initials: CE
authors.lastname: Pucillo
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053278:OX40 Ligand; D051966:Phospholipase C gamma / Q000378:metabolism*; D053262:Receptors, OX40 / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D048069:Tumor Necrosis Factors / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D048069:Tumor Necrosis Factors; D051966:Phospholipase C gamma; D002118:Calcium