title: Mast cells are essential intermediaries in regulatory T-cell tolerance.
abstract: Contrary to the proinflammatory role of mast cells in allergic disorders, the results obtained in this study establish that mast cells are essential in CD4+CD25+Foxp3+ regulatory T (T(Reg))-cell-dependent peripheral tolerance. Here we confirm that tolerant allografts, which are sustained owing to the immunosuppressive effects of T(Reg) cells, acquire a unique genetic signature dominated by the expression of mast-cell-gene products. We also show that mast cells are crucial for allograft tolerance, through the inability to induce tolerance in mast-cell-deficient mice. High levels of interleukin (IL)-9--a mast cell growth and activation factor--are produced by activated T(Reg) cells, and IL-9 production seems important in mast cell recruitment to, and activation in, tolerant tissue. Our data indicate that IL-9 represents the functional link through which activated T(Reg) cells recruit and activate mast cells to mediate regional immune suppression, because neutralization of IL-9 greatly accelerates allograft rejection in tolerant mice. Finally, immunohistochemical analysis clearly demonstrates the existence of this novel T(Reg)-IL-9-mast cell relationship within tolerant allografts.
authors.affiliation: Department of Microbiology & Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, New Hampshire 03756, USA.
authors.forename: Li-Fan
authors.initials: LF
authors.lastname: Lu
authors.forename: Evan F
authors.initials: EF
authors.lastname: Lind
authors.forename: David C
authors.initials: DC
authors.lastname: Gondek
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Bennett
authors.forename: Michael W
authors.initials: MW
authors.lastname: Gleeson
authors.forename: Karina
authors.initials: K
authors.lastname: Pino-Lagos
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Scott
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Coyle
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Reed
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Snick
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
authors.forename: Xin Xiao
authors.initials: XX
authors.lastname: Zheng
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Noelle
mesh_terms: D000818:Animals; D002452:Cell Count; D005786:Gene Expression Regulation / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D016906:Interleukin-9 / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D012867:Skin / Q000166:cytology / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D016906:Interleukin-9