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Gitta Stockinger group project:

Plasticity of CD4 effector T cell development

Since the discovery of Th1 and Th2 effector T cell subsets 20 years ago, inducible regulatory T cells (iTreg) and Th17 T cells were added to the portfolio of helper T cells. It is unclear how many more effector T cell subsets there may be and to what degree their characteristics are fixed or flexible.

We recently described that TGF-β, a cytokine with an astonishing range of functions reprograms Th2 cells to losing their characteristic profile and switch to interleukin 9 (IL-9) secretion. TGF-β in combination with IL-4 can also drive differentiation of IL-9 producing T cells from naïve precursors, suggesting there may be another subset, “Th9”. Thus, TGF-β constitutes a regulatory switch that in combination with other cytokines can re-program effector T cell differentiation along different pathways.

We are using cytokine 'fate' reporter models to facilitate visualisation and isolation of cells that have committed to particular cytokine expression to study their plasticity in different inflammatory models in vivo.

Selected publications

Hirota, K; Duarte, JH; Veldhoen, M; Hornsby, E; Li, Y; Cua, DJ; Ahlfors, H; Wilhelm, C; Tolaini, M; Menzel, U; Garefalaki, A; Potocnik, AJ and Stockinger, B (2011)
Fate mapping of IL-17-producing T cells in inflammatory responses.
Nature Immunology 12, 255-264 PubMed abstract
Veldhoen, M; Hocking, RJ; Atkins, CJ; Locksley, RM and Stockinger, B (2006)
TGFß in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells.
Immunity 24, 179-189 PubMed abstract