PMID- 27244900
OWN - NLM
STAT- MEDLINE
DCOM- 20171116
LR  - 20211204
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 8
IP  - 6
DP  - 2016 Jun
TI  - Retinoic acid treated human dendritic cells induce T regulatory cells via the 
      expression of CD141 and GARP which is impaired with age.
PG  - 1223-35
LID - 10.18632/aging.100973 [doi]
AB  - Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid 
      (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic 
      cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs 
      from aged and young individuals to RA with a view to understand the role of DCs 
      in age-associated increased susceptibility to mucosal diseases. Our 
      investigations revealed that compared to young DCs, RA stimulated DCs from aged 
      subjects are defective in inducing IL-10 and T regulatory cells. Examinations of 
      the underlying mechanisms indicated that RA exposure led to the upregulation of 
      CD141 and GARP on DCs which rendered the DCs tolerogenic. CD141(hi), GARP(+) DCs 
      displayed enhanced capacity to induce T regulatory cells compared to CD141(lo) 
      and GARP(-) DCs. Unlike RA stimulated DCs from young, DCs from aged subjects 
      exhibited diminished upregulation of both CD141 and GARP. The percentage of DCs 
      expressing CD141 and GARP on RA treatment was significantly reduced in DCs from 
      aged individuals. Furthermore, the remaining CD141(hi), GARP(+) DCs from aged 
      individuals were also deficient in inducing T regs. In summary, reduced response 
      of aged DCs to RA enhances mucosal inflammation in the elderly, increasing their 
      susceptibility to mucosal diseases.
FAU - Agrawal, Sudhanshu
AU  - Agrawal S
AD  - Division of Basic and Clinical Immunology, Department of Medicine, University of 
      California, Irvine, CA 92697, USA.
FAU - Ganguly, Sreerupa
AU  - Ganguly S
AD  - Division of Basic and Clinical Immunology, Department of Medicine, University of 
      California, Irvine, CA 92697, USA.
FAU - Tran, Alexander
AU  - Tran A
AD  - Division of Basic and Clinical Immunology, Department of Medicine, University of 
      California, Irvine, CA 92697, USA.
FAU - Sundaram, Padmaja
AU  - Sundaram P
AD  - Division of Basic and Clinical Immunology, Department of Medicine, University of 
      California, Irvine, CA 92697, USA.
FAU - Agrawal, Anshu
AU  - Agrawal A
AD  - Division of Basic and Clinical Immunology, Department of Medicine, University of 
      California, Irvine, CA 92697, USA.
LA  - eng
GR  - R01 AG045216/AG/NIA NIH HHS/United States
GR  - UL1 TR000153/TR/NCATS NIH HHS/United States
GR  - UL1 TR001414/TR/NCATS NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Antigens, Surface)
RN  - 0 (IL10 protein, human)
RN  - 0 (LRRC32 protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (THBD protein, human)
RN  - 0 (Thrombomodulin)
RN  - 130068-27-8 (Interleukin-10)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/*metabolism
MH  - Antigens, Surface/*metabolism
MH  - Dendritic Cells/*drug effects/metabolism
MH  - Female
MH  - Humans
MH  - Interleukin-10/metabolism
MH  - Male
MH  - Membrane Proteins/*metabolism
MH  - Middle Aged
MH  - T-Lymphocytes, Regulatory/*drug effects/metabolism
MH  - Thrombomodulin
MH  - Tretinoin/*pharmacology
MH  - Young Adult
PMC - PMC4931828
OTO - NOTNLM
OT  - GARP
OT  - T regulatory cells
OT  - aging
OT  - dendritic cells
OT  - retinoic acid
COIS- Conflict of interest statement The authors declare no conflict of interest.
EDAT- 2016/06/01 06:00
MHDA- 2017/11/29 06:00
PMCR- 2016/06/01
CRDT- 2016/06/01 06:00
PHST- 2016/03/28 00:00 [received]
PHST- 2016/05/16 00:00 [accepted]
PHST- 2016/06/01 06:00 [entrez]
PHST- 2016/06/01 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 100973 [pii]
AID - 10.18632/aging.100973 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2016 Jun;8(6):1223-35. doi: 10.18632/aging.100973.