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, G. Mikala, T. Masszi, E. Búzás, Z. Pós

Research output: Article

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. 1 2018

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Cathepsin K
Protease Inhibitors
Skin
Graft vs Host Disease
Granzymes
Cholecalciferol
Recycling
Type C Phospholipases
Peptidyl-Dipeptidase A
Microarray Analysis
Flow Cytometry
Leukocytes
Peptide Hydrolases
B-Lymphocytes
Down-Regulation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Skin-homing CD8+ T cells preferentially express GPI-anchored peptidase inhibitor 16, an inhibitor of cathepsin K. / Lupsa, Nikolett; Érsek, Barbara; Horváth, Andor; Bencsik, András; Lajkó, Eszter; Silló, Pálma; Oszvald, Ádám; Wiener, Zoltán; Reményi, Péter; Mikala, G.; Masszi, T.; Búzás, E.; Pós, Z.

In: European Journal of Immunology, Vol. 48, No. 12, 01.12.2018, p. 1944-1957.

Research output: Article

Lupsa, Nikolett ; Érsek, Barbara ; Horváth, Andor ; Bencsik, András ; Lajkó, Eszter ; Silló, Pálma ; Oszvald, Ádám ; Wiener, Zoltán ; Reményi, Péter ; Mikala, G. ; Masszi, T. ; Búzás, E. ; Pós, Z. / Skin-homing CD8+ T cells preferentially express GPI-anchored peptidase inhibitor 16, an inhibitor of cathepsin K. In: European Journal of Immunology. 2018 ; Vol. 48, No. 12. pp. 1944-1957.
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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.",
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AU - Lupsa, Nikolett

AU - Érsek, Barbara

AU - Horváth, Andor

AU - Bencsik, András

AU - Lajkó, Eszter

AU - Silló, Pálma

AU - Oszvald, Ádám

AU - Wiener, Zoltán

AU - Reményi, Péter

AU - Mikala, G.

AU - Masszi, T.

AU - Búzás, E.

AU - Pós, Z.

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N2 - 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.

AB - 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.

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KW - Skin

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