PMID- 19536139
OWN - NLM
STAT- MEDLINE
DCOM- 20091207
LR  - 20220325
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 129
IP  - 12
DP  - 2009 Dec
TI  - Identification of glucocorticoid-induced TNF receptor-related protein ligand on 
      keratinocytes: ligation by GITR induces keratinocyte chemokine production and 
      augments T-cell proliferation.
PG  - 2784-94
LID - 10.1038/jid.2009.163 [doi]
AB  - Glucocorticoid-induced tumor necrosis factor (TNF) receptor-related protein 
      ligand (GITRL) is a recently described co-stimulatory molecule expressed by 
      antigen-presenting cells (APCs). Activated keratinocytes are known to engage 
      intraepithelial T cells through co-stimulatory molecules. This study investigated 
      the expression and function of GITRL in resting keratinocytes. We showed by 
      immunofluorescence and flow cytometry that keratinocytes from Balb/C and C57Bl/6 
      mice, as well as PAM 212 murine cell line keratinocytes and human epidermal 
      keratinocytes (HEK), express cell-surface GITRL. Stimulation of murine skin 
      biopsies and HEK with GITR fusion protein (GITR: Fc FP) resulted in mRNA 
      induction for chemoattractants: cutaneous T-cell-attracting chemokine (CTACK), 
      thymus and activation-regulated chemokine (TARC), IL-8, monocyte chemoattractant 
      protein-1 (MCP-1), and murine beta-defensin 3 (MBD3). Immunofluorescent studies 
      on mouse biopsies treated with GITR: Fc FP confirmed corresponding TARC and MCP-1 
      protein production by keratinocytes. Chemokine induction was shown to be 
      NF-kappaB-mediated. T-cell proliferation was enhanced by the addition of 
      keratinocytes. This was reversed by pretreatment with an anti-GITRL antibody. We 
      conclude that keratinocytes express GITRL, and that through this important 
      co-stimulatory molecule, they have the potential to influence T-cell numbers in 
      the skin through chemokine production and through a direct cell-cell effect on 
      T-cell proliferation.
FAU - Byrne, Aideen M
AU  - Byrne AM
AD  - Department of Pediatrics, National Jewish Health, Denver, Colorado, USA.
FAU - Goleva, Elena
AU  - Goleva E
FAU - Leung, Donald Y M
AU  - Leung DY
LA  - eng
GR  - R01 AR041256/AR/NIAMS NIH HHS/United States
GR  - U01 AI147462/AI/NIAID NIH HHS/United States
GR  - AR41256/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090618
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Antibodies)
RN  - 0 (Ccl17 protein, mouse)
RN  - 0 (Ccl27a protein, mouse)
RN  - 0 (Chemokine CCL17)
RN  - 0 (Chemokine CCL27)
RN  - 0 (Glucocorticoid-Induced TNFR-Related Protein)
RN  - 0 (Interleukin-8)
RN  - 0 (Ligands)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tnfrsf18 protein, mouse)
RN  - 0 (Tnfsf18 protein, mouse)
RN  - 0 (Tumor Necrosis Factors)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - CD4-Positive T-Lymphocytes/*cytology/immunology/metabolism
MH  - Cell Communication/immunology
MH  - Cell Division/immunology
MH  - Cells, Cultured
MH  - Chemokine CCL17/genetics/metabolism
MH  - Chemokine CCL27/genetics/metabolism
MH  - Epidermal Cells
MH  - Epidermis/immunology
MH  - Glucocorticoid-Induced TNFR-Related Protein
MH  - Humans
MH  - Interleukin-8/genetics/metabolism
MH  - Keratinocytes/*cytology/*immunology/metabolism
MH  - Kidney/cytology
MH  - Ligands
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, Nerve Growth Factor/immunology/*metabolism
MH  - Receptors, Tumor Necrosis Factor/immunology/*metabolism
MH  - Signal Transduction/immunology
MH  - Spleen/cytology
MH  - Tumor Necrosis Factors/immunology/*metabolism
PMC - PMC8609662
MID - NIHMS1754092
COIS- CONFLICT OF INTEREST The authors state no conflict of interest.
EDAT- 2009/06/19 09:00
MHDA- 2009/12/16 06:00
PMCR- 2021/11/23
CRDT- 2009/06/19 09:00
PHST- 2009/06/19 09:00 [entrez]
PHST- 2009/06/19 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2021/11/23 00:00 [pmc-release]
AID - S0022-202X(15)34168-3 [pii]
AID - 10.1038/jid.2009.163 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2009 Dec;129(12):2784-94. doi: 10.1038/jid.2009.163. Epub 2009 
      Jun 18.