title: CD73 is a phenotypic marker of effector memory Th17 cells in inflammatory bowel disease.
abstract: Purinergic signaling and associated ectonucleotidases, such as CD39 and CD73, have been implicated in the pathogenesis of inflammatory bowel disease (IBD). CD39 is known to be a Treg memory cell marker, and here we determine the phenotype and function of CD73(+) CD4(+)  T lymphocytes in patients with IBD. We describe elevated levels of CD73(+) CD4(+)  T cells in the peripheral blood and intestinal lamina propria of patients with active IBD. The functional phenotype of these CD73(+) CD4(+)  T cells was further determined by gene expression, ecto-enzymatic activity, and suppressive assays. Increased numbers of CD73(+) CD4(+)  T cells in the periphery and lamina propria were noted during active inflammation, which returned to baseline levels following anti-TNF treatment. Peripheral CD73(+) CD4(+)  T cells predominantly expressed CD45RO, and were enriched with IL-17A(+)  cells. The CD73(+) CD4(+)  cell population expressed higher levels of RORC, IL-17A, and TNF, and lower levels of FOXP3 and/or CD25, than CD73(-) CD4(+)  T cells. Expression of CD73 by peripheral CD4(+)  T cells was increased by TNF, and decreased by an anti-TNF monoclonal antibody (infliximab). In vitro, these peripheral CD73(+) CD4(+)  T cells did not suppress proliferation of CD25(-)  effector cells, and expressed higher levels of pro-inflammatory markers. We conclude that the CD73(+) CD4(+)  T-cell population in patients with active IBD are enriched with cells with a T-helper type 17 phenotype, and could be used to monitor disease activity during treatment.
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Glen A
authors.initials: GA
authors.lastname: Doherty
authors.forename: Aiping
authors.initials: A
authors.lastname: Bai
authors.forename: Dusan
authors.initials: D
authors.lastname: Hanidziar
authors.forename: Maria S
authors.initials: MS
authors.lastname: Longhi
authors.forename: Garrett O
authors.initials: GO
authors.lastname: Lawlor
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Putheti
authors.forename: Eva
authors.initials: E
authors.lastname: Csizmadia
authors.forename: Martina
authors.initials: M
authors.lastname: Nowak
authors.forename: Adam S
authors.initials: AS
authors.lastname: Cheifetz
authors.forename: Alan C
authors.initials: AC
authors.lastname: Moss
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
mesh_terms: D015720:5'-Nucleotidase / Q000097:blood / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000097:blood / Q000276:immunology; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000276:immunology*; D000069285:Infliximab; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D058851:GPI-Linked Proteins; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D015720:5'-Nucleotidase; C548241:NT5E protein, human