title: Lamina Propria CD4+LAP+ Regulatory T Cells Are Increased in Active Ulcerative Colitis but Show Increased IL-17 Expression and Reduced Suppressor Activity.
abstract: BACKGROUND
  A CD4+CD25- regulatory T cell population expressing the surface TGF-β in its latent form LAP+ [latency associated peptide] cells was proved to be protective in experimental colitis and to be suppressive of human peripheral blood [PB] T proliferation. We investigated the frequency and function of lamina propria [LP] CD4+LAP+ T cells in inflammatory bowel disease [IBD] patients.
  
  
  METHODS
  Specimens from patients undergoing colonoscopy or bowel resection for IBD and colonic cancer were used as source of lamina propria mononuclear cells [LPMC]. The ulcerative colitis [UC] group was divided according to endoscopic activity evaluated with modified Baron Score. IL-17, IFN-γ, IL-10, LAP, and Foxp3 expression in CD3+CD8- [CD4] or CD3+/CD4+ gated cell population was assessed by immunofluorescence. The ability of FACS-sorted LP CD3+CD8-[CD4] LAP+CD25- to inhibit stimulated autologous PB CD3+CD8-[CD4] LAP- CD25- cells proliferation was assessed.
  
  
  RESULTS
  LP CD4LAP+ cells were significantly increased, when compared with controls, in active UC patients and not in Crohn's disease patients. The majority of LP CD4+LAP+ cells were Foxp3-. The percentage of IL-17+ cells in LP CD3+CD8-[CD4] LAP+ cells was significantly higher in active UC patients when compared with controls. LP CD3+CD8-[CD4]LAP+CD25- isolated from UC patients showed reduced or no ability to inhibit autologous PB CD3+CD8-[CD4]LAP-CD25- cell proliferation when compared with controls. Removal of IL-17+ cells from LP CD3+CD8-[CD4] LAP+ cells increases their suppressive ability.
  
  
  CONCLUSIONS
  The percentage of LP CD4LAP+ cells is increased in active UC, showing reduced suppressor activity due to their increased proportion of intracellular IL-17 expression.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanita, Roma, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: D'Ambrosio
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanita, Roma, Italy Department of Internal Medicine and Medical Specialties,, University 'Sapienza,' Roma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossu
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanita, Roma, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Amendola
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanita, Roma, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zandri
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanita, Roma, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Butera
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Sanchez
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Biffoni
authors.affiliation: Department of General Surgery, 'P. Stefanini', University 'Sapienza', Roma, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Pronio
authors.affiliation: Department of General Surgery, 'P. Stefanini', University 'Sapienza', Roma, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Montesani
authors.affiliation: Division of Gastroenterology, Azienda Ospedaliera S. Camillo-Forlanini, Roma, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Kohn
authors.affiliation: IBD, GE Unit, Sandro Pertini Hospital, Roma, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Pica
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanita, Roma, Italy monica.boirivant@iss.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Boirivant
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D049109:Cell Proliferation; D003093:Colitis, Ulcerative / Q000276:immunology*; D003106:Colon / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology*; D005260:Female; D006801:Humans; D007082:Ileum / Q000276:immunology; D020381:Interleukin-17 / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D020381:Interleukin-17; D010455:Peptides; D011498:Protein Precursors; D016212:Transforming Growth Factor beta; C472416:latency-associated propeptide, TGF-beta
keywords: IL-17; Inflammatory bowel disease; regulatory CD4+LAP+ cells