DC activated via dectin-1 convert Treg into IL-17 producers.
Th cells producing IL-17 play a pro-inflammatory role at mucosal surfaces. Treg at the same sites dampen inflammation and prevent immunopathology. Th cells producing IL-17 (Th17) and Treg are thought to be distinct populations defined by expression of the transcription factors ROR-gammat and Foxp3, respectively. Here, we show that mouse CD25(+)Foxp3(+) Treg can be converted into a hybrid T-cell population characterized by the expression of Foxp3 and ROR-gammat and the production of IL-17. Conversion was observed upon coculture with DC selectively activated via dectin-1, a C-type lectin receptor involved in fungal recognition, and depended on IL-23 produced by DC. Within the Foxp3(+) population, only Foxp3(+)ROR-gammat(+) T cells but not Foxp3(+)ROR-gammat(-)-T cells become Foxp3(+)IL-17(+) T cells. These results indicate that some Foxp3(+) T cells can produce IL-17 while retaining Foxp3 expression and suggest that Treg could play an unexpected pro-inflammatory role in some settings.
Osorio
Fabiola
F
Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London, UK.
LeibundGut-Landmann
Salomé
S
Lochner
Matthias
M
Lahl
Katharina
K
Sparwasser
Tim
T
Eberl
Gérard
G
Reis e Sousa
Caetano
C
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D053759:Interleukin-23 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D000099181:Dectin-1
D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D053645:Interleukin-2 Receptor alpha Subunit; D053759:Interleukin-23; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000099181:Dectin-1; C498833:Foxp3 protein, mouse