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  • Journal article
    Murugananthan AU, Bernardo DO, Mann ER, Tee CT, Hart AL, Arebi N, Knight SC, Al-Hassi HOet al., 2012,

    ILEAL AND COLONIC MUCOSAL DENDRITIC CELL CYTOKINE PROFILES DIFFER AT REST AND AFTER IN VITRO BACTERIA AND PRO-BIOTIC CHALLENGE IN POSTOPERATIVE CROHN'S DISEASE PATIENTS

    , GUT, Vol: 61, Pages: A168-A168, ISSN: 0017-5749
  • Journal article
    Peake STC, Bernardo D, Mann ER, Al-Hassi HO, Knight SC, Hart ALet al., 2012,

    Mechanisms of action of anti-tumor necrosis factor alpha agents in Crohn’s disease

    , Inflamm Bowel Dis
  • Journal article
    Bernardo D, Mann ER, Al-Hassi HO, Clark SK, McCarthy NE, Milestone AN, Cochrane SA, Hart AL, Stagg AJ, Knight SCet al., 2012,

    Human gut-specific homeostatic dendritic cells are generated from blood precursors by the gut microenvironment.

    , Inflammatory Bowel Diseases, Vol: 7, Pages: 1275-1286

    BACKGROUND: Dendritic cells (DC) dictate not only the type of T-cell immunity, but also homing patterns of T cells in mice. In humans, we characterized normal human gut DC and tested whether gut-specific homeostatic DC could be generated from blood precursors by factors in the gut microenvironment.METHODS: We characterized the phenotype and function of healthy human gut DC compared with blood and skin DC, and studied whether conditioning of blood DC in the presence of colonic biopsy supernatants (Bx-SN) induced gut-like phenotype and functions.RESULTS: Blood DC mostly expressed both gut and skin homing markers, indicating potential to migrate to both major immune surface organs, and induced multi-homing T cells. However, DC within gut or skin did not demonstrate this multi-homing phenotype, were tissue-specific, and induced tissue-specific T cells. Human gut DC were less stimulatory for allogeneic T cells than their dermal and blood counterparts. Human blood DC cultured in vitro lost homing marker expression. Conditioning of human enriched blood DC with colonic Bx-SN from healthy controls induced a gut-homing phenotype and a homeostatic profile. Moreover, Bx-SN-conditioned DC demonstrated a restricted T-cell stimulatory capacity and preferentially induced gut-specific T cells. Retinoic acid and transforming growth factor beta (TGF-β) mediated the acquisition of the gut-homing and homeostatic properties, respectively, induced by colonic Bx-SN on blood enriched DC.CONCLUSIONS: Tissue-specific factors manipulate immunity via modulating characteristics of DC and may provide tools to generate tissue-specific immunotherapy. (Inflamm Bowel Dis 2011;).
  • Journal article
    Bernardo D, Vallejo-Díez S, Mann ER, Al-Hassi HO, Martínez-Abad B, Montalvillo E, Tee CT, Murugananthan AU, Núñez H, Peake STC, Hart AL, Fernández-Salazar L, Garrote JA, Arranz E, Knight SCet al., 2012,

    IL-6 controls the intestinal inflammation in human ulcerative colitis and mediates the conditioning of dendritic cells towards a pro-inflammatory phenotype with increased skin-homing phenotype and skin-imprinting capacity on T-cells

    , European Journal of Immunology
  • Journal article
    Bernardo D, Peake STC, Knight SC, Hart ALet al., 2012,

    Homing marker expression on circulating dendritic cells correlates with different phenotypes of Crohn’s disease

    , Journal of Crohn’s and Colitis
  • Journal article
    Bernardo D, Al-Hassi HO, Mann ER, Tee CT, Murugananthan AU, Peake STC, Hart AL, Knight SCet al., 2012,

    T-cell proliferation and FoxP3 expression in human T-cells are dependent on T-cell density: physics of a confined space?

    , Human Imunology

    T-cell proliferation rates in vitro depend on factors including initial T-cell number, dose of stimulus, culture time, and available physical space. The role of forkhead box P3 (FoxP3) in the identification of T cells with a regulatory phenotype remains controversial in humans. Through 5-carboxyfluorescein diacetate succinimidyl ester labeling of human T cells and subsequent culture of different numbers of T cells and antigen-presenting cells (APC), we studied proliferative T-cell responses and FoxP3 expression in divided T cells. T-cell proliferation rates depended on initial T-cell/APC numbers. Proliferation rates decreased when high initial T-cell numbers were increased. FoxP3 expression was expressed exclusively in virtually all divided T cells cultured at high T-cell densities, irrespective of their CD4 nature or cytokine content, and was coexpressed with T-bet. However, when T cells were cultured on larger surfaces or at lower initial numbers, FoxP3 expression was not induced in divided T cells, even when most of the cells had undergone cell division. FoxP3(+) T cells generated at high cell densities did not elicit a suppressive phenotype and FoxP3 expression was subsequently lost in time when the stimulus was removed. Therefore, caution should be observed in the use of FoxP3 expression to identify regulatory T cells in humans because its expression may be only a consequence of activation status in a restricted environment.
  • Conference paper
    Mann E, Jialu Y, Bernardo D, Al-Hassi HO, Hart A, Thomas L, Tee C, Daulatzai N, Landy J, Peake S, Yaqoob P, Knight Set al., 2011,

    Probiotic strain <i>Lactobacillus casei</i> Shirota imprints a skin-homing profile on effector T-cells and exhibits dual mechanisms of immunoregulation

    , Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 194-194, ISSN: 0019-2805
  • Conference paper
    Bernardo D, Vallejo-Diez S, Mann ER, Al-Hassi HO, Martinez-Abad B, Montalvillo E, Tee CT, Murugananthan AU, Nunez H, Hart AL, Fernandez-Salazar L, Garrote JA, Arranz E, Knight SCet al., 2011,

    Intestinal homeostatic signals are lost in affected areas of ulcerative colitis patients inducing an abnormal skin homing phenotype in dendritic cells and T-cells they stimulate

    , Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 144-144, ISSN: 0019-2805
  • Conference paper
    Bernardo D, Al-Hassi HO, Mann ER, Tee CT, Murugananthan AU, Hart AL, Knight SCet al., 2011,

    FoxP3 expression in human stimulated T-cells is transient and dependent on T-cell density -still a valid marker for identification of human regulatory T-cells?

    , Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL, Pages: 196-196, ISSN: 0019-2805
  • Journal article
    Ng SC, Benjamin JL, McCarthy NE, Hedin CRH, Koutsoumpas A, Plamondon S, Price CL, Hart AL, Kamm MA, Forbes A, Knight SC, Lindsay JO, Whelan K, Stagg AJet al., 2011,

    Relationship Between Human Intestinal Dendritic Cells, Gut Microbiota, and Disease Activity in Crohn's Disease

    , INFLAMMATORY BOWEL DISEASES, Vol: 17, Pages: 2027-2037, ISSN: 1078-0998

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