PMID- 22551553
OWN - NLM
STAT- MEDLINE
DCOM- 20120814
LR  - 20171116
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 188
IP  - 11
DP  - 2012 Jun 1
TI  - Integrin CD11b negatively regulates TLR9-triggered dendritic cell cross-priming 
      by upregulating microRNA-146a.
PG  - 5293-302
LID - 10.4049/jimmunol.1102371 [doi]
AB  - Dendritic cells (DCs) play critical roles in cross-priming to induce the CTL 
      response against infection; however, the molecular mechanisms for the regulation 
      of DC cross-priming need to be investigated further, which may help to improve 
      the potency of DC vaccines through engineering modifications. Our previous 
      studies showed that beta2 integrin CD11b could control TLR-triggered NK cell 
      cytotoxicity and macrophage inflammatory responses. CD11b is also abundantly 
      expressed in DCs, but it is unknown whether CD11b participates in the regulation 
      of DC cross-priming for the CTL response. Also, because microRNAs (miRNAs) are 
      important regulators of the immune response, it remains unclear whether miRNAs 
      are regulated by CD11b in DCs. In this study, we showed that CD11b deficiency 
      upregulated TLR9-triggered, but not TLR4-triggered, IL-12p70 production in DCs, 
      subsequently promoting DC cross-priming of the CTL response. Further experiments 
      showed that CD11b selectively promoted TLR9-triggered miR-146a upregulation in 
      DCs by sustaining late-phase NF-kappaB activation. Additionally, Notch1, a known 
      positive regulator of IL-12p70 production in DCs, was confirmed to be directly 
      targeted by miR-146a. miR-146a upregulation and Notch1 repression were determined 
      to be responsible for the reduced IL-12p70 production in TLR9-triggered wild-type 
      DCs compared with that in CD11b-deficient DCs. Therefore, CD11b and downstream 
      miR-146a may be new negative regulators for DC cross-priming by suppressing 
      Notch1 expression and IL-12p70 production. Our data indicate a new mechanism for 
      the regulation of DC cross-priming through integrins and miRNAs.
FAU - Bai, Yi
AU  - Bai Y
AD  - National Key Laboratory of Medical Immunology, Institute of Immunology, Second 
      Military Medical University, Shanghai 200433, China.
FAU - Qian, Cheng
AU  - Qian C
FAU - Qian, Li
AU  - Qian L
FAU - Ma, Feng
AU  - Ma F
FAU - Hou, Jin
AU  - Hou J
FAU - Chen, Yongjian
AU  - Chen Y
FAU - Wang, Qingqing
AU  - Wang Q
FAU - Cao, Xuetao
AU  - Cao X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120502
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CD11b Antigen)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn146 microRNA, mouse)
RN  - 0 (Notch1 protein, mouse)
RN  - 0 (Receptor, Notch1)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 9)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Animals
MH  - CD11b Antigen/genetics/*physiology
MH  - Cells, Cultured
MH  - Cross-Priming/*immunology
MH  - Dendritic Cells/*immunology/metabolism
MH  - Down-Regulation/*immunology
MH  - HEK293 Cells
MH  - Humans
MH  - Interleukin-12/antagonists & inhibitors/biosynthesis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - MicroRNAs/*biosynthesis
MH  - Receptor, Notch1/antagonists & inhibitors/biosynthesis
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Toll-Like Receptor 9/*antagonists & inhibitors/*physiology
MH  - Up-Regulation/*immunology
EDAT- 2012/05/04 06:00
MHDA- 2012/08/15 06:00
CRDT- 2012/05/04 06:00
PHST- 2012/05/04 06:00 [entrez]
PHST- 2012/05/04 06:00 [pubmed]
PHST- 2012/08/15 06:00 [medline]
AID - jimmunol.1102371 [pii]
AID - 10.4049/jimmunol.1102371 [doi]
PST - ppublish
SO  - J Immunol. 2012 Jun 1;188(11):5293-302. doi: 10.4049/jimmunol.1102371. Epub 2012 
      May 2.