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

► 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 analysi...

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Bibliographic Details
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
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Summary:	► 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0008-8749 1090-2163
DOI:	10.1016/j.cellimm.2012.04.002