title: Signaling events involved in interleukin 27 (IL-27)-induced proliferation of human naive CD4+ T cells and B cells.
abstract: IL-27 induces stronger proliferation of naive than memory human B cells and CD4(+) T cells. In B cells, this differential response is associated with similar levels of IL-27 receptor chains, IL-27Rα and gp130, in both subsets and stronger STAT1 and STAT3 activation by IL-27 in naive B cells. Here, we show that the stronger proliferative response of CD3-stimulated naive CD4(+) T cells to IL-27 is associated with lower levels of IL-27Rα but higher levels of gp130 compared with memory CD4(+) T cells. IL-27 signaling differs between naive and memory CD4(+) T cells, as shown by more sustained STAT1, -3, and -5 activation and weaker activation of SHP-2 in naive CD4(+) T cells. In the latter, IL-27 increases G0/G1 to S phase transition, cell division and, in some cases, cell survival. IL-27 proliferative effect on naive CD4(+) T cells is independent of MAPK, but is dependent on c-Myc and Pim-1 induction by IL-27 and is associated with induction of cyclin D2, cyclin D3, and CDK4 by IL-27 in a c-Myc and Pim-1-dependent manner. In BCR-stimulated naive B cells, IL-27 only increases entry in the S phase and induces the expression of Pim-1 and of cyclins A, D2, and D3. In these cells, inhibition of Pim-1 inhibits IL-27 effect on proliferation and cyclin induction. Altogether, these data indicate that IL-27 mediates proliferation of naive CD4(+) T cells and B cells through induction of both common and distinct sets of cell cycle regulators.
authors.affiliation: CNRS UMR 8147, Université Paris Descartes, 75015 Paris, France.
authors.forename: Pascaline
authors.initials: P
authors.lastname: Charlot-Rabiega
authors.forename: Emilie
authors.initials: E
authors.lastname: Bardel
authors.forename: Céline
authors.initials: C
authors.lastname: Dietrich
authors.forename: Robert
authors.initials: R
authors.lastname: Kastelein
authors.forename: Odile
authors.initials: O
authors.lastname: Devergne
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002453:Cell Cycle; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D020381:Interleukin-17