Skin-homing CD8 + T cells preferentially express GPI-anchored peptidase inhibitor 16, an inhibitor of cathepsin K

Nikolett Lupsa, Barbara Érsek, Andor Horváth, András Bencsik, Eszter Lajkó, Pálma Silló, Ádám Oszvald, Zoltán Wiener, Péter Reményi, Gábor Mikala, Tamás Masszi, Edit I. Buzás, Zoltán Pós

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 (CD8β + /CLA + ), gut-homing (CD8β + /integrinβ7 + ), and reference (CD8β + /CLA /integrinβ7 ) 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.

Original languageEnglish
Pages (from-to)1944-1957
Number of pages14
JournalEuropean journal of immunology
Volume48
Issue number12
DOIs
Publication statusPublished - Dec 2018

Keywords

  • CD8 T cell
  • GvHD
  • Homing
  • PI16
  • Skin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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