title: Modulation of Cytokine Secretion Allows CD4 T Cells Secreting IL-10 and IL-17 to Simultaneously Participate in Maintaining Tolerance and Immunity.
abstract: CD4 T cells secreting IL-10 or IL-17 are frequent at mucosal sites, where their equilibrium is important for simultaneously maintaining tolerance and immunity to the resident microbiota. The mode of action of these cells, however, is as yet incompletely understood. In this study, we have combined ex vivo analysis of CD4 T cells producing IL-10 or/and IL-17 with assessment of clonal populations isolated ex vivo using a cytokine catch assay. We found that circulating CD4 T cells secreting IL-10 or/and IL-17 ex vivo include both conventional FOXP3- CD4 T cells and FOXP3+ Helios- Treg. Upon assessment of clonal populations derived from single ex vivo isolated cytokine secreting cells, we found that IL-10 or/and IL-17 secreting cells prevalently secrete one or the other cytokine depending on the type of stimulation, the time after stimulation and the presence of microbial products. Namely, IL-10 secretion by clonal cells was prevalent at early time points after TCR mediated stimulation, was independent of co-stimulation and was increased in the presence of the microbial fermentation product butyrate. In contrast, IL-17 secretion was higher at later time points after TCR mediated stimulation and in the presence of co-stimulatory signals. Taken together, these results provide insights into the mechanisms that, through modulation of cytokine secretion depending on conditions, allow IL-10 and IL-17 producing CD4 T cells to contribute to maintain tolerance to microbes locally, while retaining the ability to participate in protective immune responses at distant sites.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1102, Equipe Labellisée Ligue Contre le Cancer, Institut de Cancérologie de l'Ouest, Nantes-Saint Herblain, France.
authors.forename: Kanako
authors.initials: K
authors.lastname: Saito
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1102, Equipe Labellisée Ligue Contre le Cancer, Institut de Cancérologie de l'Ouest, Nantes-Saint Herblain, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Pignon
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1102, Equipe Labellisée Ligue Contre le Cancer, Institut de Cancérologie de l'Ouest, Nantes-Saint Herblain, France.
authors.forename: Maha
authors.initials: M
authors.lastname: Ayyoub
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1102, Equipe Labellisée Ligue Contre le Cancer, Institut de Cancérologie de l'Ouest, Nantes-Saint Herblain, France.|Faculty of Medicine, University of Nantes, Nantes, France.
authors.forename: Danila
authors.initials: D
authors.lastname: Valmori
mesh_terms: D020148:Butyric Acid / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D006801:Humans; D051740:Ikaros Transcription Factor / Q000378:metabolism; D007108:Immune Tolerance; D007156:Immunologic Memory; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C111431:IKZF2 protein, human; C508609:IL10 protein, human; D020381:Interleukin-17; D020148:Butyric Acid; D016753:Interleukin-10; D051740:Ikaros Transcription Factor