title: CCR6(-) regulatory T cells blunt the restoration of gut Th17 cells along the CCR6-CCL20 axis in treated HIV-1-infected individuals.
abstract: The gut CD4(+) T cells, particularly the T helper type 17 (Th17) subset, are not completely restored in most HIV-1-infected individuals despite combined antiretroviral therapy, when initiated at the chronic phase of infection. We show here that the CCR6-CCL20 chemotactic axis is altered, with reduced CCL20 production by small intestine epithelial cells in treated HIV-1-infected individuals. This leads to impaired CCR6(+)CD4(+) T-cell homing, particularly Th17 cells, to the small intestine mucosa. In contrast, the frequency of gut FoxP3(+) T regulatory (Treg) cells, specifically the CCR6(-) subset, was increased. The resulting imbalance in the Th17/CCR6(-) Treg ratio and the associated shift from interleukin (IL)-17 to IL-10 and transforming growth factor-β (TGF-β) blunts CCL20 production by enterocytes, perpetuating a negative feedback for the recruitment of CCR6(+)CD4(+) T cells to the small intestine in treated HIV-1-infected individuals.
authors.affiliation: INSERM, UMR1043, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Loiseau
authors.affiliation: CHU de Toulouse, Laboratoire de Virologie, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Requena
authors.affiliation: Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mavigner
authors.affiliation: INSERM, UMR1043, Toulouse, France.|CHU de Toulouse, Laboratoire de Virologie, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Cazabat
authors.affiliation: Université Toulouse III Paul Sabatier, Toulouse, France.|CHU de Toulouse, Service de Chirurgie Générale et Digestive, Toulouse, France.
authors.forename: N
authors.initials: N
authors.lastname: Carrere
authors.affiliation: Université Toulouse III Paul Sabatier, Toulouse, France.|CHU de Toulouse, Service de Chirurgie Générale et Digestive, Toulouse, France.
authors.forename: B
authors.initials: B
authors.lastname: Suc
authors.affiliation: CHU de Toulouse, Service de Gastro-Entérologie et Hépatologie-Pôle Digestif, Toulouse, France.
authors.forename: K
authors.initials: K
authors.lastname: Barange
authors.affiliation: Université Toulouse III Paul Sabatier, Toulouse, France.|CHU de Toulouse, Service de Médecine Interne-Pôle Digestif, Toulouse, France.|IRD UMR152, Toulouse, France.
authors.forename: L
authors.initials: L
authors.lastname: Alric
authors.affiliation: Université Toulouse III Paul Sabatier, Toulouse, France.|CHU de Toulouse, Service des Maladies Infectieuses et Tropicales, Toulouse, France.
authors.forename: B
authors.initials: B
authors.lastname: Marchou
authors.affiliation: Université Toulouse III Paul Sabatier, Toulouse, France.|CHU de Toulouse, Service des Maladies Infectieuses et Tropicales, Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Massip
authors.affiliation: INSERM, UMR1043, Toulouse, France.|CHU de Toulouse, Laboratoire de Virologie, Toulouse, France.|Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: J
authors.initials: J
authors.lastname: Izopet
authors.affiliation: INSERM, UMR1043, Toulouse, France.|Université Toulouse III Paul Sabatier, Toulouse, France.|CHU de Toulouse, Service des Maladies Infectieuses et Tropicales, Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Delobel
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D054418:Chemokine CCL20 / Q000235:genetics / Q000276:immunology*; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D020895:Enterocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D025461:Feedback, Physiological; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000821:virology; D007421:Intestine, Small / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D054399:Receptors, CCR6 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
chemical_list: D019380:Anti-HIV Agents; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D015704:CD4 Antigens; D054418:Chemokine CCL20; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508609:IL10 protein, human; D020381:Interleukin-17; D054399:Receptors, CCR6; D016212:Transforming Growth Factor beta; D016753:Interleukin-10