PMID- 31175164
OWN - NLM
STAT- MEDLINE
DCOM- 20200214
LR  - 20200214
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 203
IP  - 2
DP  - 2019 Jul 15
TI  - Signaling Cascade through DC-ASGPR Induces Transcriptionally Active CREB for 
      IL-10 Induction and Immune Regulation.
PG  - 389-399
LID - 10.4049/jimmunol.1900289 [doi]
AB  - The types and magnitude of Ag-specific immune responses can be determined by the 
      functional plasticity of dendritic cells (DCs). However, how DCs display 
      functional plasticity and control host immune responses have not been fully 
      understood. In this study, we report that ligation of DC-asialoglycoprotein 
      receptor (DC-ASGPR), a C-type lectin receptor (CLR) expressed on human DCs, 
      resulted in rapid activation of Syk, followed by PLCgamma2 and PKCdelta engagements. 
      However, different from other Syk-coupled CLRs, including Dectin-1, signaling 
      cascade through DC-ASGPR did not trigger NF-kappaB activation. Instead, it 
      selectively activated MAPK ERK1/2 and JNK. Rapid and prolonged phosphorylation of 
      ERK1/2 led to sequential activation of p90RSK and CREB, which consequently bound 
      to IL10 promoter and initiated cytokine expression. In addition, DC-ASGPR 
      ligation activated Akt, which differentially regulated the activities of GSK-3alpha/beta 
      and beta-catenin and further contributed to IL-10 expression. Our observations 
      demonstrate that DC-ASGPR induces IL-10 expression via an intrinsic signaling 
      pathway, which provides a molecular explanation for DC-ASGPR-mediated programing 
      of DCs to control host immune responses.
CI  - Copyright (c) 2019 by The American Association of Immunologists, Inc.
FAU - Gu, Chao
AU  - Gu C
AD  - Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259.
AD  - Institute of Biomedical Studies, Baylor University, Waco, TX 76712; and.
FAU - Wang, Lei
AU  - Wang L
AUID- ORCID: 0000-0001-9143-4354
AD  - Baylor Institute for Immunology Research, Dallas, TX 75204.
FAU - Zurawski, Sandra
AU  - Zurawski S
AD  - Baylor Institute for Immunology Research, Dallas, TX 75204.
FAU - Oh, SangKon
AU  - Oh S
AD  - Department of Immunology, Mayo Clinic, Scottsdale, AZ 85259; Oh.SangKon@mayo.edu.
AD  - Institute of Biomedical Studies, Baylor University, Waco, TX 76712; and.
LA  - eng
GR  - R01 AI105066/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190607
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Asialoglycoprotein Receptor)
RN  - 0 (CREB1 protein, human)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Cytokines)
RN  - 0 (IL10 protein, human)
RN  - 0 (Immunologic Factors)
RN  - 0 (Lectins, C-Type)
RN  - 0 (NF-kappa B)
RN  - 0 (dectin 1)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Asialoglycoprotein Receptor/*immunology
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/*immunology
MH  - Cytokines/immunology
MH  - Dendritic Cells/immunology
MH  - Humans
MH  - Immunologic Factors/immunology
MH  - Interleukin-10/*immunology
MH  - Lectins, C-Type/immunology
MH  - MAP Kinase Signaling System/immunology
MH  - NF-kappa B/immunology
MH  - Phosphorylation/immunology
MH  - Promoter Regions, Genetic/immunology
MH  - Signal Transduction/*immunology
MH  - Transcriptional Activation/*immunology
EDAT- 2019/06/09 06:00
MHDA- 2020/02/15 06:00
CRDT- 2019/06/09 06:00
PHST- 2019/03/11 00:00 [received]
PHST- 2019/05/17 00:00 [accepted]
PHST- 2019/06/09 06:00 [pubmed]
PHST- 2020/02/15 06:00 [medline]
PHST- 2019/06/09 06:00 [entrez]
AID - jimmunol.1900289 [pii]
AID - 10.4049/jimmunol.1900289 [doi]
PST - ppublish
SO  - J Immunol. 2019 Jul 15;203(2):389-399. doi: 10.4049/jimmunol.1900289. Epub 2019 
      Jun 7.