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 FcɛRI-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 Ca2+ influx, independently of phospholipase C (PLC)-γ2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effects of Treg cells, restoring normal Ca2+ 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.
|Titolo:||CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction|
|Parole Chiave:||Cell Degranulation ; Animals ; Calcium ; Cell Line, Tumor ; Gene Knockdown Techniques ; Histamine Release ; Humans ; Hypersensitivity ; Mast Cells ; Membrane Glycoproteins ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Phospholipase C gamma ; Receptors, OX40 ; T-Lymphocytes, Regulatory ; Tumor Necrosis Factors|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||14-nov-2008|
|Digital Object Identifier (DOI):||10.1016/j.immuni.2008.08.018|
|Appare nelle tipologie:||01 - Articolo su periodico|