title: Human gut-specific homeostatic dendritic cells are generated from blood precursors by the gut microenvironment.
abstract: 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.
authors: Antigen Presentation Research Group, Imperial College London, Northwick Park and St. Mark's Campus, Harrow, UK.
authors: Elizabeth R
authors: ER
authors: Mann
authors: David
authors: D
authors: Bernardo
authors: Hafid Omar
authors: HO
authors: Al-Hassi
authors: Nicholas R
authors: NR
authors: English
authors: Susan K
authors: SK
authors: Clark
authors: Neil E
authors: NE
authors: McCarthy
authors: Andrew N
authors: AN
authors: Milestone
authors: Stella A
authors: SA
authors: Cochrane
authors: Ailsa L
authors: AL
authors: Hart
authors: Andrew J
authors: AJ
authors: Stagg
authors: Stella C
authors: SC
authors: Knight
mesh_terms: D000328:Adult; D000368:Aged; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010641:Phenotype; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D016201:Receptors, Lymphocyte Homing; D016212:Transforming Growth Factor beta; D014212:Tretinoin