title: Trib3 is regulated by IL-3 and affects bone marrow-derived mast cell survival and function.
abstract: Mast cells are the principal effectors of IgE-mediated immune responses, including allergic reactions. Tribbles homolog 3 (Trib3) encodes a pseudokinase implicated in the cellular stress response and has been linked to inflammation in certain situations. Here we report the role of Trib3 in mouse bone marrow-derived mast cells (BMMCs). Our results show that Trib3 mRNA expression in BMMCs is positively regulated by the growth factor interleukin (IL)-3. BMMCs originating from Trib3 knockout mice demonstrate unaltered differentiation kinetics and cell surface expression of mast cell markers. When challenged with transient IL-3 deprivation, Trib3-deficient BMMCs display delayed recovery, and during prolonged IL-3 starvation, cell death is accelerated in Trib3-null cultures. IgE-dependent and pharmacologically induced degranulation is impaired in Trib3-deficient BMMCs, as is activation-induced cytokine mRNA expression. Thus, Trib3 contributes to the survival and activity of primary cultured mast cells, which suggests a role for Trib3 in the modulation of the immune response.
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. tord@ebc.ee
authors.forename: Tiit
authors.initials: T
authors.lastname: Ord
authors.forename: Daima
authors.initials: D
authors.lastname: Ord
authors.forename: Sulev
authors.initials: S
authors.lastname: Kuuse
authors.forename: Mario
authors.initials: M
authors.lastname: Plaas
authors.forename: Tõnis
authors.initials: T
authors.lastname: Ord
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015550:Cell Degranulation / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D007073:Immunoglobulin E / Q000276:immunology; D007377:Interleukin-3 / Q000172:deficiency / Q000494:pharmacology* / Q000502:physiology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010323:Passive Cutaneous Anaphylaxis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018797:Cell Cycle Proteins; D007377:Interleukin-3; D012333:RNA, Messenger; C474830:TRB3 protein, mouse; D007073:Immunoglobulin E