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

• Published in: Cellular immunology Vol. 275; no. 1-2; pp. 12 - 18
• Main Authors: Nicholson, Ian C., Mavrangelos, Christos, Bird, Daniel R.G., Bresatz-Atkins, Suzanne, Eastaff-Leung, Nicola G., Grose, Randall H., Gundsambuu, Batjargal, Hill, Danika, Millard, Debbrah J., Sadlon, Timothy J., To, Sarah, Zola, Heddy, Barry, Simon C., Krumbiegel, Doreen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-01-2012
• Subjects: Carrier Proteins - immunology; CCL17 protein; CCL20 protein; CCR6 protein; CD25 antigen; CD4 antigen; Cell migration; Cell Movement; Cell Proliferation; Chemokine CCL17 - immunology; Chemokine CCL20 - immunology; Chemokine receptors; Cytokines - immunology; Forkhead Transcription Factors - immunology; Foxp3 protein; Glycoproteins - immunology; Helper cells; Humans; Immunologic Memory; Inflammation; Leukocyte Common Antigens - immunology; Lymphocyte migration; Lymphocytes T; Memory; Memory Treg; Monoclonal antibodies; peptidase; Peptidase inhibitor 16; Phenotype; Phenotyping; Regulatory T cells; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; Memory Treg; Lymphocyte migration; Regulatory T cells; Peptidase inhibitor 16
• DOI: 10.1016/j.cellimm.2012.04.002
• EISSN: 1090-2163
• ISSN: 0008-8749

► PI16 is over-expressed by Treg compared with other Th cells. ► PI16-expressing Treg have a memory phenotype and express high levels of FOXP3. ► PI16-expressing Treg preferentially migrate toward the chemokines CCL17 and CCL20.
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.