PMID- 16111635
OWN - NLM
STAT- MEDLINE
DCOM- 20051005
LR  - 20231213
IS  - 1074-7613 (Print)
IS  - 1074-7613 (Linking)
VI  - 23
IP  - 2
DP  - 2005 Aug
TI  - Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside 
      modification and the evolutionary origin of RNA.
PG  - 165-75
AB  - DNA and RNA stimulate the mammalian innate immune system through activation of 
      Toll-like receptors (TLRs). DNA containing methylated CpG motifs, however, is not 
      stimulatory. Selected nucleosides in naturally occurring RNA are also methylated 
      or otherwise modified, but the immunomodulatory effects of these alterations 
      remain untested. We show that RNA signals through human TLR3, TLR7, and TLR8, but 
      incorporation of modified nucleosides m5C, m6A, m5U, s2U, or pseudouridine 
      ablates activity. Dendritic cells (DCs) exposed to such modified RNA express 
      significantly less cytokines and activation markers than those treated with 
      unmodified RNA. DCs and TLR-expressing cells are potently activated by bacterial 
      and mitochondrial RNA, but not by mammalian total RNA, which is abundant in 
      modified nucleosides. We conclude that nucleoside modifications suppress the 
      potential of RNA to activate DCs. The innate immune system may therefore detect 
      RNA lacking nucleoside modification as a means of selectively responding to 
      bacteria or necrotic tissue.
FAU - Kariko, Katalin
AU  - Kariko K
AD  - Department of Neurosurgery, University of Pennsylvania School of Medicine, 
      Philadelphia, 19104, USA. kariko@mail.med.upenn.edu
FAU - Buckstein, Michael
AU  - Buckstein M
FAU - Ni, Houping
AU  - Ni H
FAU - Weissman, Drew
AU  - Weissman D
LA  - eng
GR  - AI060505/AI/NIAID NIH HHS/United States
GR  - AI50484/AI/NIAID NIH HHS/United States
GR  - DE14825/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Antigens, CD)
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Immunoglobulins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nucleosides)
RN  - 0 (Phosphatidylethanolamines)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (TLR3 protein, human)
RN  - 0 (TLR7 protein, human)
RN  - 0 (TLR8 protein, human)
RN  - 0 (Toll-Like Receptor 3)
RN  - 0 (Toll-Like Receptor 7)
RN  - 0 (Toll-Like Receptor 8)
RN  - 0 (Toll-Like Receptors)
RN  - 63231-63-0 (RNA)
RN  - 76391-83-8 (1,2-dielaidoylphosphatidylethanolamine)
SB  - IM
CIN - Immunity. 2005 Aug;23(2):111-3. PMID: 16111629
MH  - Antigens, CD
MH  - Biomarkers
MH  - Cell Line
MH  - Cytokines/metabolism
MH  - Dendritic Cells/drug effects/immunology/metabolism
MH  - *Evolution, Molecular
MH  - HLA-DR Antigens/immunology
MH  - Humans
MH  - Immunoglobulins/immunology
MH  - Membrane Glycoproteins/immunology/*physiology
MH  - Nucleosides/*metabolism
MH  - Phosphatidylethanolamines/pharmacology
MH  - RNA/antagonists & inhibitors/genetics/*metabolism
MH  - Receptors, Cell Surface/*physiology
MH  - Signal Transduction/genetics/*physiology
MH  - Toll-Like Receptor 3
MH  - Toll-Like Receptor 7
MH  - Toll-Like Receptor 8
MH  - Toll-Like Receptors
MH  - CD83 Antigen
EDAT- 2005/08/23 09:00
MHDA- 2005/10/06 09:00
CRDT- 2005/08/23 09:00
PHST- 2005/01/14 00:00 [received]
PHST- 2005/05/26 00:00 [revised]
PHST- 2005/06/15 00:00 [accepted]
PHST- 2005/08/23 09:00 [pubmed]
PHST- 2005/10/06 09:00 [medline]
PHST- 2005/08/23 09:00 [entrez]
AID - S1074-7613(05)00211-6 [pii]
AID - 10.1016/j.immuni.2005.06.008 [doi]
PST - ppublish
SO  - Immunity. 2005 Aug;23(2):165-75. doi: 10.1016/j.immuni.2005.06.008.