title: Mast cell FcεRI-induced early growth response 2 regulates CC chemokine ligand 1-dependent CD4+ T cell migration.
abstract: Mast cells are well positioned in host tissue for detecting environmental signals, including allergens, leading to activation of the high-affinity IgE receptor FcεRI, and initiating a signaling cascade that perpetuates the production of biologically potent mediators, including chemokines. We have identified a novel target of mast cell FcεRI activity in the transcription factor early growth response 2 (Egr2) and sought to characterize its function therein. Egr2 was transiently activated following FcεRI-mediated signaling, targeted the promoter of the chemokine CCL1, and was critical for allergen-induced mast cell CCL1 production. Egr2-deficient mast cells were incapable of directing CD4(+) T cell migration via the CCL1-CCR8 axis. In a model of allergic asthma, reconstitution of mast cell-deficient mice with Egr2-deficient mast cells demonstrated that mast cell Egr2 was essential for migration of CD4(+) T cells to the inflamed lung. These findings position Egr2 as a critical regulator of mast cell-directed CD4(+) T cell migration.
authors.affiliation: Department of Microbiology and Immunology, Dalhousie University and Izaak Walton Killam Health Centre, Halifax, Nova Scotia B3K 6R8, Canada.
authors.forename: Zhengli
authors.initials: Z
authors.lastname: Wu
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Macneil
authors.forename: Robert
authors.initials: R
authors.lastname: Junkins
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Jason N
authors.initials: JN
authors.lastname: Berman
authors.forename: Tong-Jun
authors.initials: TJ
authors.lastname: Lin
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054402:Chemokine CCL1 / Q000276:immunology*; D051767:Early Growth Response Protein 2 / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000276:immunology; D054401:Receptors, CCR8 / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology*
chemical_list: D000485:Allergens; C502258:Ccl1 protein, mouse; C489319:Ccr8 protein, mouse; D054402:Chemokine CCL1; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D054401:Receptors, CCR8; D017455:Receptors, IgE