Genetic proof for the transient nature of the Th17 phenotype.
IL-17-producing CD4(+) T cells (Th17) have been classified as a new T helper cell subset. Using an IL-17 fate mapping mouse strain, which genetically fixes the memory of IL-17 expression, we demonstrate that IL-17A/F-expressing T helper cells generated either in vitro or in vivo are not a stable T-cell subset. Upon adoptive transfer of IL-17F-reporter-positive Th17 cells to RAG-deficient or WT animals, encephalitogenic Th17 cells partially lose IL-17 expression and upregulate IFN-γ. Additionally, we show that Th1 cells can convert in vivo to IL-17A/IFN-γ-coexpressing cells in the mesenteric lymph nodes (mLN). Our data classify IL-17A and IL-17F as cytokines produced transiently in response to the local microenvironment, thus showing that IL-17 expression does not define an end-stage T helper cell subset.
Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany. kurschus@uni-mainz.de
Florian C
FC
Kurschus
Andrew L
AL
Croxford
André P
AP
Heinen
Simone
S
Wörtge
Daniele
D
Ielo
Ari
A
Waisman
D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D016654:Genes, RAG-1 / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D019426:Integrases / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; C045073:Cre recombinase; D019426:Integrases