title: PI16 is expressed by a subset of human memory Treg with enhanced migration to CCL17 and CCL20.
abstract: The peptidase inhibitor PI16 was shown previously by microarray analysis to be over-expressed by CD4-positive/CD25-positive Treg compared with CD4-positive/CD25-negative Th cells. Using a monoclonal antibody to the human PI16 protein, we found that PI16-positive Treg have a memory (CD45RO-positive) phenotype and express higher levels of FOXP3 than PI16-negative Treg. PI16-positive Treg are functional in suppressor assays in vitro with potency similar to PI16-negative Treg. Further phenotyping of the PI16-positive Treg revealed that the chemokine receptors CCR4 and CCR6 are expressed by more of the PI16-positive/CD45RO-positive Treg compared with PI16-negative/CD45RO-positive Treg or Th cells. PI16-positive Treg showed enhanced in vitro migration towards the inflammatory chemokines CCL17 and CCL20, suggesting they can migrate to sites of inflammation. We conclude that PI16 identifies a novel distinct subset of functional memory Treg which can migrate to sites of inflammation and regulate the pro-inflammatory response at those sites.
authors.affiliation: Women's and Children's Health Research Institute, 72 King William Road, North Adelaide, South Australia, 5006, Australia.
authors.forename: Ian C
authors.initials: IC
authors.lastname: Nicholson
authors.forename: Christos
authors.initials: C
authors.lastname: Mavrangelos
authors.forename: Daniel R G
authors.initials: DR
authors.lastname: Bird
authors.forename: Suzanne
authors.initials: S
authors.lastname: Bresatz-Atkins
authors.forename: Nicola G
authors.initials: NG
authors.lastname: Eastaff-Leung
authors.forename: Randall H
authors.initials: RH
authors.lastname: Grose
authors.forename: Batjargal
authors.initials: B
authors.lastname: Gundsambuu
authors.forename: Danika
authors.initials: D
authors.lastname: Hill
authors.forename: Debbrah J
authors.initials: DJ
authors.lastname: Millard
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Sadlon
authors.forename: Sarah
authors.initials: S
authors.lastname: To
authors.forename: Heddy
authors.initials: H
authors.lastname: Zola
authors.forename: Simon C
authors.initials: SC
authors.lastname: Barry
authors.forename: Doreen
authors.initials: D
authors.lastname: Krumbiegel
mesh_terms: D002352:Carrier Proteins / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D054414:Chemokine CCL17 / Q000276:immunology*; D054418:Chemokine CCL20 / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000276:immunology; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
chemical_list: C106230:CCL17 protein, human; C108355:CCL20 protein, human; D002352:Carrier Proteins; D054414:Chemokine CCL17; D054418:Chemokine CCL20; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006023:Glycoproteins; C501293:PI16 protein, human; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human