PMID- 22539302 OWN - NLM STAT- MEDLINE DCOM- 20120706 LR - 20181201 IS - 1521-4141 (Electronic) IS - 0014-2980 (Linking) VI - 42 IP - 5 DP - 2012 May TI - IL-6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and Tcells they stimulate. PG - 1337-53 LID - 10.1002/eji.201142327 [doi] AB - 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. CI - (c) 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Bernardo, David AU - Bernardo D AD - Antigen Presentation Research Group, Imperial College London, Northwick Park & St Mark's Campus, Watford Road, Harrow, United Kingdom. FAU - Vallejo-Diez, Sara AU - Vallejo-Diez S FAU - Mann, Elizabeth R AU - Mann ER FAU - Al-Hassi, Hafid O AU - Al-Hassi HO FAU - Martinez-Abad, Beatriz AU - Martinez-Abad B FAU - Montalvillo, Enrique AU - Montalvillo E FAU - Tee, Cheng T AU - Tee CT FAU - Murugananthan, Aravinth U AU - Murugananthan AU FAU - Nunez, Henar AU - Nunez H FAU - Peake, Simon T C AU - Peake ST FAU - Hart, Ailsa L AU - Hart AL FAU - Fernandez-Salazar, Luis AU - Fernandez-Salazar L FAU - Garrote, Jose A AU - Garrote JA FAU - Arranz, Eduardo AU - Arranz E FAU - Knight, Stella C AU - Knight SC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Cytokines) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-13) RN - 0 (Interleukin-6) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Cells, Cultured MH - Colitis, Ulcerative/*immunology MH - Cytokines/analysis/immunology/metabolism MH - Dendritic Cells/*immunology MH - Female MH - Humans MH - Inflammation/immunology MH - Interleukin-13/immunology MH - Interleukin-6/*immunology MH - Male MH - Middle Aged MH - Severity of Illness Index MH - Skin/*immunology MH - T-Lymphocytes/*immunology MH - Th2 Cells/immunology EDAT- 2012/04/28 06:00 MHDA- 2012/07/07 06:00 CRDT- 2012/04/28 06:00 PHST- 2012/04/28 06:00 [entrez] PHST- 2012/04/28 06:00 [pubmed] PHST- 2012/07/07 06:00 [medline] AID - 10.1002/eji.201142327 [doi] PST - ppublish SO - Eur J Immunol. 2012 May;42(5):1337-53. doi: 10.1002/eji.201142327.