PMID- 17513740
OWN - NLM
STAT- MEDLINE
DCOM- 20070712
LR  - 20220330
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 178
IP  - 11
DP  - 2007 Jun 1
TI  - Altered innate immune functioning of dendritic cells in elderly humans: a role of 
      phosphoinositide 3-kinase-signaling pathway.
PG  - 6912-22
AB  - Aging represents a state of paradox where chronic inflammation is associated with 
      declining immune responses. Dendritic cells (DCs) are the major APCs responsible 
      for initiating an immune response. However, DC functions in aging have not been 
      studied in detail. In this study, we have compared the innate immune functions of 
      monocyte-derived myeloid DCs from elderly subjects with DCs from young 
      individuals. We show that although phenotypically comparable, DCs from the aging 
      are functionally different from DCs from the young. In contrast to DCs from the 
      young, DCs from elderly individuals display 1) significantly reduced capacity to 
      phagocytose Ags via macropinocytosis and endocytosis as determined by flow 
      cytometry; 2) impaired capacity to migrate in vitro in response to the chemokines 
      MIP-3beta and stromal cell-derived factor-1; and 3) significantly increased LPS 
      and ssRNA-induced secretion of TNF-alpha and IL-6, as determined by ELISA. 
      Investigations of intracellular signaling revealed reduced phosphorylation of AKT 
      in DCs from the aging, indirectly suggesting decreased activation of the PI3K 
      pathway. Because the PI3K-signaling pathway plays a positive regulatory role in 
      phagocytosis and migration, and also functions as a negative regulator of TLR 
      signaling by inducing activation of p38 MAPK, this may explain the aberrant 
      innate immune functioning of DCs from elderly subjects. Results from real-time 
      PCR and protein expression by flow cytometry demonstrated an increased expression 
      of phosphatase and tensin homolog, a negative regulator of the PI3K-signaling 
      pathway, in DCs from the aging. Increased phosphatase and tensin homolog may thus 
      be responsible for the defect in AKT phosphorylation and, therefore, the altered 
      innate immune response of DCs from elderly humans.
FAU - Agrawal, Anshu
AU  - Agrawal A
AD  - Division of Basic and Clinical Immunology, University of California, Irvine, CA 
      92697, USA. aagrawal@uci.edu
FAU - Agrawal, Sudhanshu
AU  - Agrawal S
FAU - Cao, Jia-Ning
AU  - Cao JN
FAU - Su, Houfen
AU  - Su H
FAU - Osann, Kathryn
AU  - Osann K
FAU - Gupta, Sudhir
AU  - Gupta S
LA  - eng
GR  - AG027512/AG/NIA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/*immunology
MH  - Cell Count
MH  - Cell Differentiation/immunology
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Dendritic Cells/cytology/*enzymology/*immunology/metabolism
MH  - Humans
MH  - *Immunity, Innate
MH  - Inflammation Mediators/metabolism
MH  - Jurkat Cells
MH  - Monocytes/cytology/enzymology/immunology
MH  - PTEN Phosphohydrolase/biosynthesis
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Signal Transduction/*immunology
MH  - Up-Regulation/immunology
EDAT- 2007/05/22 09:00
MHDA- 2007/07/13 09:00
CRDT- 2007/05/22 09:00
PHST- 2007/05/22 09:00 [pubmed]
PHST- 2007/07/13 09:00 [medline]
PHST- 2007/05/22 09:00 [entrez]
AID - 178/11/6912 [pii]
AID - 10.4049/jimmunol.178.11.6912 [doi]
PST - ppublish
SO  - J Immunol. 2007 Jun 1;178(11):6912-22. doi: 10.4049/jimmunol.178.11.6912.