PI16 is expressed by a subset of human memory Treg with enhanced migration to CCL17 and CCL20

Cell Immunol. Jan-Feb 2012;275(1-2):12-8. doi: 10.1016/j.cellimm.2012.04.002. Epub 2012 Apr 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / immunology*
  • Cell Movement*
  • Cell Proliferation
  • Chemokine CCL17 / immunology*
  • Chemokine CCL20 / immunology*
  • Cytokines / immunology
  • Forkhead Transcription Factors / immunology
  • Glycoproteins / immunology*
  • Humans
  • Immunologic Memory*
  • Leukocyte Common Antigens / immunology
  • Phenotype
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • CCL17 protein, human
  • CCL20 protein, human
  • Carrier Proteins
  • Chemokine CCL17
  • Chemokine CCL20
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Glycoproteins
  • PI16 protein, human
  • Leukocyte Common Antigens
  • PTPRC protein, human