%0 Journal Article
%T Diversity and flexibility of Th17 effector functions
%A Thomas Kamradt
%A Hyun-Dong Chang
%J Arthritis Research & Therapy
%D 2011
%I BioMed Central
%R 10.1186/ar3296
%X Cytokines produced by CD4+ T-helper (Th) lymphocytes are critical for protective and pathogenic immune responses. According to their cytokine production, Th cells can be categorised into at least four functionally distinct lineages, called Th1, Th2, Th17, and Treg. Differentiation of naive Th cells is induced upon antigen recognition in the presence of instructive cytokines, resulting in the upregulation of so-called master transcription factors - that is, T-bet, GATA-3, retinoic acid-related orphan receptor ¦Ãt (ROR¦Ãt), or FoxP3 for Th1, Th2, Th17, or Treg cells, respectively - and imprinting of functionally relevant genes, such as genes encoding for cytokines and chemokine receptors [1,2].Th17 cells were originally characterised by their co-expression of IL-17 (also called IL-17A) together with IL-17F, TNF¦Á, granulocyte-macrophage colony-stimulating factor, and lymphotactin, but not Th1 or Th2 cytokines [3,4]. Over the past several years it has become clear that Th17 cells do not represent a homogeneous lineage. IL-17 can be coexpressed with a variety of other cytokines including IL-21, IL-22, IFN¦Ã, IL-10, and IL-4, with consequences for the cells' functionality [1,2,5-7]. Moreover, IL-17 is not exclusively produced by CD4+ cells but also by CD8+ T cells, ¦Ã¦Ä T cells, natural killer T cells, natural killer cells, and perhaps also neutrophils, mast cells, and others [2]. Not all IL-17 producers therefore are Th17 cells. One possible current definition of Th17 cells would be CD4+ Th cells that express IL-17A, the IL-23 receptor, and CCR6, and have high levels of expression of the transcription factor ROR¦Ãt in the absence of significant expression of other lineage-specific transcription factors and cytokines. In humans, CD161 expression has been described as a surface marker for Th17 cells [7].IL-17A and IL-17F are highly homologous (50% amino acid identity) and share the same receptor. Yet they perform distinct functions. IL-17A seems to be more relevant for the devel
%U http://arthritis-research.com/content/13/2/106