Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the T(H)17 lineage-specific transcription factor RORgamma t.
Recent studies have suggested a close relationship between CD4(+)FOXP3(+) regulatory T cells (Tregs) and proinflammatory IL-17-producing T helper cells (T(H)17) expressing the lineage-specific transcription factor RORgamma t. We report here the unexpected finding that human memory Tregs secrete IL-17 ex vivo and constitutively express RORgamma t. IL-17-secreting Tregs share some phenotypic and functional features with conventional T(H)17 cells, expressing high levels of CCR4 and CCR6 and low levels of CXCR3. However, unlike conventional T(H)17 cells, they express low levels of CD161 and mostly fail to cosecrete IL-22 and TNF-alpha ex vivo. Ex vivo secretion of IL-17 and constitutive expression of RORgamma t by human memory Tregs suggest that, in addition to their well-known suppressive functions, these cells likely play additional, as yet undescribed, proinflammatory functions.
Ayyoub
Maha
M
Institut National de la Santé et de la Recherche Médicale, Unité 892, Centre René Gauducheau, 44800 Saint Herblain, France. maha.ayyoub@univ-nantes.fr
Deknuydt
Florence
F
Raimbaud
Isabelle
I
Dousset
Christelle
C
Leveque
Lucie
L
Bioley
Gilles
G
Valmori
Danila
D
D019070:Cell Lineage / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010641:Phenotype; D018168:Receptors, Retinoic Acid / Q000276:immunology*; D011988:Receptors, Thyroid Hormone / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone