title: IL-6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and Tcells they stimulate.
abstract: Dendritic cells (DCs) control the type and location of immune responses. Ulcerative colitis (UC) is considered a Th2 disease mediated by IL-13 where up to one third of patients can develop extraintestinal manifestations. Colonic biopsies from inflamed and noninflamed areas of UC patients were cultured in vitro and their supernatants were used to condition human blood enriched DCs from healthy controls. Levels of IL-13 in the culture supernatants were below the detection limit in most cases and the cytokine profile suggested a mixed profile rather than a Th2 cytokine profile. IL-6 was the predominant cytokine found in inflamed areas from UC patients and its concentration correlated with the Mayo endoscopic score for severity of disease. DCs conditioned with noninflamed culture supernatants acquired a regulatory phenotype with decreased stimulatory capacity. However, DCs conditioned with inflamed culture supernatants acquired a proinflammatory phenotype with increased expression of the skin-homing chemokine CCR8. These DCs did not have decreased T-cell stimulatory capacity and primed T cells with the skin-homing CLA molecule in an IL-6-dependent mechanism. Our results highlight the role of IL-6 in UC and question the concept of UC as a Th2 disease and the relevance of IL-13 in its etiology.
authors.affiliation: Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, Watford Road, Harrow, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Bernardo
authors.forename: Sara
authors.initials: S
authors.lastname: Vallejo-Díez
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Mann
authors.forename: Hafid O
authors.initials: HO
authors.lastname: Al-Hassi
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martínez-Abad
authors.forename: Enrique
authors.initials: E
authors.lastname: Montalvillo
authors.forename: Cheng T
authors.initials: CT
authors.lastname: Tee
authors.forename: Aravinth U
authors.initials: AU
authors.lastname: Murugananthan
authors.forename: Henar
authors.initials: H
authors.lastname: Núñez
authors.forename: Simon T C
authors.initials: ST
authors.lastname: Peake
authors.forename: Ailsa L
authors.initials: AL
authors.lastname: Hart
authors.forename: Luis
authors.initials: L
authors.lastname: Fernández-Salazar
authors.forename: Jose A
authors.initials: JA
authors.lastname: Garrote
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arranz
authors.forename: Stella C
authors.initials: SC
authors.lastname: Knight
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology*; D016207:Cytokines / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018793:Interleukin-13 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D018793:Interleukin-13; D015850:Interleukin-6