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
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.
Available from: PubMed Central
- "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 . These T cells produce large amounts of IL-17 and are increased in psoriasis and Crohn's disease. "
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ABSTRACT: Several clinical studies have demonstrated that the humanized anti-interleukin-6 (IL-6) receptor antibody tocilizumab (TCZ) improves clinical symptoms and prevents progression of joint destruction in rheumatoid arthritis (RA). However, the precise mechanism by which IL-6 blockade leads to the improvement of RA is not well understood. IL-6 promotes synovitis by inducing neovascularization, infiltration of inflammatory cells, and synovial hyperplasia. IL-6 causes bone resorption by inducing osteoclast formation via the induction of RANKL in synovial cells, and cartilage degeneration by producing matrix metalloproteinases (MMPs) in synovial cells and chondrocytes. Moreover, IL-6 is involved in autoimmunity by altering the balance between T(h)17 cells and T(reg). IL-6 also acts on changing lipid concentrations in blood and on inducing the production of hepcidin which causes iron-deficient anemia. In conclusion, IL-6 is a major player in the pathogenesis of RA, and current evidence indicates that the blockade of IL-6 is a beneficial therapy for RA patients.
05/2011; 2011(2090-1984):765624. DOI:10.1155/2011/765624
Available from: Hyun-Dong Chang
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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
Available from: Shabaana A Khader
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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