title: Ex vivo IL-1 receptor type I expression in human CD4+ T cells identifies an early intermediate in the differentiation of Th17 from FOXP3+ naive regulatory T cells.
abstract: IL-17-producing CD4(+) Th (Th17) cells are a unique subset of proinflammatory cells expressing the retinoic acid-related orphan receptor γt and associated with different forms of inflammatory autoimmune pathologies. The development of Th17 cells, mediated by TGF-β and IL-1, is closely related to that of FOXP3(+) suppressor/regulatory T cells (Treg). In this study, we report that ex vivo expression of IL-1RI in human circulating CD4(+) T cells identifies a subpopulation of FOXP3(+) Treg that coexpress retinoic acid-related orphan receptor γt, secrete IL-17, and are highly enriched among CCR7(+) central memory cells. Consistent with the concept that IL-1RI expression in Treg identifies a subpopulation at an early stage of differentiation, we show that, in Th17 populations differentiated in vitro from natural naive FOXP3(+) Treg, IL-1RI(+) IL-17-secreting cells are central memory cells, whereas IL-1RI(-) cells secreting IL-17 are effector memory cells. Together with the absence of detectable IL-1RI and IL-17 expression in resting naive CD4(+) T cells, these data identify circulating CCR7(+) Treg expressing IL-1RI ex vivo as early intermediates along an IL-1-controlled differentiation pathway leading from naive FOXP3(+) Treg to Th17 effectors. We further show that, whereas IL-1RI(+) central memory Treg respond to stimulation in the presence of IL-1 by generating IL-17-secreting effectors, a significant fraction of them maintain FOXP3 expression, consistent with an important role of this population in maintaining the Treg/Th17 memory pool in vivo.
authors: INSERM, Unité 892, Centre de Lutte Contre le Cancer René Gauducheau, 44800 Saint Herblain, France.
authors: Caroline
authors: C
authors: Raffin
authors: Isabelle
authors: I
authors: Raimbaud
authors: Danila
authors: D
authors: Valmori
authors: Maha
authors: M
authors: Ayyoub
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis*; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D017472:Receptors, Interleukin-1