PMID- 27655844
DCOM- 20170814
LR  - 20180123
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 197
IP  - 8
DP  - 2016 Oct 15
TI  - The Receptor for Advanced Glycation Endproducts Drives T Cell Survival and
      Inflammation in Type 1 Diabetes Mellitus.
PG  - 3076-3085
AB  - The ways in which environmental factors participate in the progression of
      autoimmune diseases are not known. After initiation, it takes years before
      hyperglycemia develops in patients at risk for type 1 diabetes (T1D). The
      receptor for advanced glycation endproducts (RAGE) is a scavenger receptor of the
      Ig family that binds damage-associated molecular patterns and advanced glycated
      endproducts and can trigger cell activation. We previously found constitutive
      intracellular RAGE expression in lymphocytes from patients with T1D. In this
      article, we show that there is increased RAGE expression in T cells from at-risk 
      euglycemic relatives who progress to T1D compared with healthy control subjects, 
      and in the CD8(+) T cells in the at-risk relatives who do versus those who do not
      progress to T1D. Detectable levels of the RAGE ligand high mobility group box 1
      were present in serum from at-risk subjects and patients with T1D. Transcriptome 
      analysis of RAGE(+) versus RAGE(-) T cells from patients with T1D showed
      differences in signaling pathways associated with increased cell activation and
      survival. Additional markers for effector memory cells and inflammatory function 
      were elevated in the RAGE(+) CD8(+) cells of T1D patients and at-risk relatives
      of patients before disease onset. These studies suggest that expression of RAGE
      in T cells of subjects progressing to disease predates dysglycemia. These
      findings imply that RAGE expression enhances the inflammatory function of T
      cells, and its increased levels observed in T1D patients may account for the
      chronic autoimmune response when damage-associated molecular patterns are
      released after cell injury and killing.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Durning, Sean P
AU  - Durning SP
AUID- ORCID: 0000-0002-5183-8802
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT
FAU - Preston-Hurlburt, Paula
AU  - Preston-Hurlburt P
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT
FAU - Clark, Paul R
AU  - Clark PR
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT
FAU - Xu, Ding
AU  - Xu D
AUID- ORCID: 0000-0001-9380-2712
AD  - Glycobiology Research and Training Center, Department of Cellular and Molecular
      Medicine, University of California, San Diego, La Jolla, CA 92093.
AD  - Department of Oral Biology, University at Buffalo, School of Dental Medicine, The
      State University of New York at Buffalo, Buffalo, NY 14214; and.
FAU - Herold, Kevan C
AU  - Herold KC
AUID- ORCID: 0000-0003-1534-6613
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT
AD  - Department of Internal Medicine, Yale University School of Medicine, New Haven,
      CT 06520.
CN  - Type 1 Diabetes TrialNet Study Group
LA  - eng
GR  - U01 DK085476/DK/NIDDK NIH HHS/United States
GR  - U01 DK061010/DK/NIDDK NIH HHS/United States
GR  - U01 DK085466/DK/NIDDK NIH HHS/United States
GR  - U01 DK103153/DK/NIDDK NIH HHS/United States
GR  - U01 DK061058/DK/NIDDK NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
GR  - R01 DK057846/DK/NIDDK NIH HHS/United States
GR  - U01 DK106984/DK/NIDDK NIH HHS/United States
GR  - P30 DK045735/DK/NIDDK NIH HHS/United States
GR  - U01 DK107014/DK/NIDDK NIH HHS/United States
GR  - U01 AI102011/AI/NIAID NIH HHS/United States
GR  - U01 DK085465/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160921
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Receptor for Advanced Glycation End Products)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Asymptomatic Diseases
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Child
MH  - Diabetes Mellitus, Type 1/*immunology
MH  - Disease Progression
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - Immunologic Memory
MH  - Inflammation/*immunology
MH  - Lymphocyte Activation
MH  - Male
MH  - Receptor for Advanced Glycation End Products/*metabolism
MH  - Risk
MH  - Signal Transduction
MH  - Up-Regulation
MH  - Young Adult
PMC - PMC5101164
MID - NIHMS814492
EDAT- 2016/09/23 06:00
MHDA- 2017/08/15 06:00
CRDT- 2016/09/23 06:00
PHST- 2016/02/05 00:00 [received]
PHST- 2016/08/18 00:00 [accepted]
PHST- 2016/09/23 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2016/09/23 06:00 [entrez]
AID - jimmunol.1600197 [pii]
AID - 10.4049/jimmunol.1600197 [doi]
PST - ppublish
SO  - J Immunol. 2016 Oct 15;197(8):3076-3085. doi: 10.4049/jimmunol.1600197. Epub 2016
      Sep 21.