title: Two functionally distinct subsets of mast cells discriminated By IL-2-independent CD25 activities.
abstract: We identified two mast cell subsets characterized by the differential expression of surface CD25 (IL-2Rα) and by different abilities to produce cytokines and to proliferate, both in vitro and in vivo. CD25 can be expressed on the surface of immune cells in the absence of the other chains of the IL-2R, which are indispensable for IL-2 signaling. We show that functional differences between the two mast cell populations were dependent on CD25 itself, which directly modulated proliferation and cytokine responses. These effects were completely independent from IL-2 or the expression of the other chains of the high-affinity IL-2R, indicating an autonomous and previously unappreciated role for CD25 in regulating cell functions. Cells genetically ablated for CD25 completely recapitulated the CD25-negative phenotype and never acquired the properties characteristic of CD25-positive mast cells. Finally, adoptive transfer experiments in the mouse demonstrated a different impact of these populations in models of anaphylaxis and contact sensitivity. Our findings indicate a general role for CD25 in contexts where IL-2 signaling is not involved, and may have important implications for all mast cell-related diseases, as well as in all cell types expressing CD25 independently of its IL-2-related functions.
authors: Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland;
authors: Lorenzo
authors: L
authors: Deho'
authors: Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland;
authors: Cristina
authors: C
authors: Leoni
authors: Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland;
authors: Tess M
authors: TM
authors: Brodie
authors: Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland;
authors: Sara
authors: S
authors: Montagner
authors: National Institute for Molecular Genetics, 20122 Milan, Italy; and.
authors: Marco
authors: M
authors: De Simone
authors: Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy.
authors: Sara
authors: S
authors: Polletti
authors: Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy.
authors: Iros
authors: I
authors: Barozzi
authors: Department of Experimental Oncology, European Institute of Oncology, 20139 Milan, Italy.
authors: Gioacchino
authors: G
authors: Natoli
authors: Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland; silvia.monticelli@irb.usi.ch.
authors: Silvia
authors: S
authors: Monticelli
mesh_terms: D016475:3T3 Cells; D000818:Animals; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: C508018:Il2ra protein, mouse; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit