Human and murine Th17

Center of Excellence for Research, Transfer, and High Education DENOthe, University of Florence, Florence, Italy.
Current opinion in HIV and AIDS (Impact Factor: 4.68). 03/2010; 5(2):114-9. DOI: 10.1097/COH.0b013e32833647c2
Source: PubMed


The purpose of this review is to summarize the most recent discoveries in the field of phenotypic and functional characterization of human and murine Th17 cells.
Human Th17 cells express CD161 and exclusively originate from CD161 precursors present in umbilical cord blood and newborn thymus in response to the combined activity of IL-1beta and IL-23. On the contrary, murine Th17 cells do not express CD161 and originate in response to IL-6, IL-1, and TGF-beta, even if the latter has recently been shown to be dispensable. Studies in mice have initially suggested that Th17 cells are the pathogenic cells in autoimmune disorders, whereas Th1 cells may behave rather as protective. Studies in humans have subsequently demonstrated the capacity of Th17 cells to shift to Th1 cells when activated in the presence of IL-12. The plasticity of Th17 to Th1 cells has been now confirmed in mice, where it was found that Th17 cells become pathogenic in some models of autoimmune diseases only when they shift to Th1 cells.
The issue of Th17 plasticity is of fundamental importance for those researchers directed to manipulate immune responses in therapeutically useful manner.

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    • "The involvement of Th17 cells in RA is, therefore, still controversial. However, the involvement of CD4+CD161+ T cells in autoimmune diseases has been attracting attention recently [46]. These T cells produce large amounts of IL-17 and are increased in psoriasis and Crohn's disease. "
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    ABSTRACT: Th1 and Th17 cells are distinct lineages of effector/memory cells, imprinted for re-expression of IFN-γ and IL-17, by upregulated expression of T-bet and retinoic acid-related orphan receptor γt (RORγt), respectively. Apparently, Th1 and Th17 cells share tasks in the control of inflammatory immune responses. Th cells coexpressing IFN-γ and IL-17 have been observed in vivo, but it remained elusive, how these cells had been generated and whether they represent a distinct lineage of Th differentiation. It has been shown that ex vivo isolated Th1 and Th17 cells are not interconvertable by TGF-β/IL-6 and IL-12, respectively. Here, we show that ex vivo isolated Th17 cells can be converted into Th1/Th17 cells by combined IFN-γ and IL-12 signaling. IFN-γ is required to upregulate expression of the IL-12Rβ2 chain, and IL-12 for Th1 polarization. These Th1/Th17 cells stably coexpress RORγt and T-bet at the single-cell level. Our results suggest a molecular pathway for the generation of Th1/Th17 cells in vivo, which combine the pro-inflammatory potential of Th1 and Th17 cells.
    European Journal of Immunology 11/2010; 40(11):3017-27. DOI:10.1002/eji.201040539 · 4.03 Impact Factor
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    Cytokine & growth factor reviews 11/2010; 21(6):403-4. DOI:10.1016/j.cytogfr.2010.10.008 · 5.36 Impact Factor
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