Skin-homing CD8+ T cells preferentially express GPI-anchored peptidase inhibitor 16, an inhibitor of cathepsin K.
Eur J Immunol
; 48(12): 1944-1957, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30365157
ABSTRACT
This study sought to identify novel CD8+ T cell homing markers by studying acute graft versus host disease (aGvHD), typically involving increased T cell homing to the skin and gut. FACS-sorted skin-homing (CD8ß+ /CLA+ ), gut-homing (CD8ß+ /integrinß7+ ), and reference (CD8ß+ /CLA- /integrinß7- ) T cells were compared in patients affected by cutaneous and/or gastrointestinal aGVHD. Microarray analysis, qPCR, and flow cytometry revealed increased expression of peptidase inhibitor 16 (PI16) in skin-homing CD8+ T cells. Robust association of PI16 with skin homing was confirmed in all types of aGvHD and in healthy controls, too. PI16 was not observed on CLA+ leukocytes other than T cells. Induction of PI16 expression on skin-homing T cells occurred independently of vitamin D3. Among skin-homing T cells, PI16 expression was most pronounced in memory-like CD45RO+ /CD127+ /CD25+ /CD69- /granzyme B- cells. PI16 was confined to the plasma membrane, was GPI-anchored, and was lost upon restimulation of memory CD8+ T cells. Loss of PI16 occurred by downregulation of PI16 transcription, and not by Phospholipase C (PLC)- or Angiotensin-converting enzyme (ACE)-mediated shedding, or by protein recycling. Inhibitor screening and pull-down experiments confirmed that PI16 inhibits cathepsin K, but may not bind to other skin proteases. These data link PI16 to skin-homing CD8+ T cells, and raise the possibility that PI16 may regulate cutaneous cathepsin K.
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MEDLINE
Assunto principal:
Pele
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Glicoproteínas
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Proteínas de Transporte
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Subpopulações de Linfócitos T
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Linfócitos T CD8-Positivos
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Doença Enxerto-Hospedeiro
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article