PMID- 34953165
OWN - NLM
STAT- MEDLINE
DCOM- 20220506
LR  - 20220506
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 34
IP  - 4
DP  - 2022 Mar 25
TI  - Selective suppression of IL-10 transcription by calcineurin in dendritic cells 
      through inactivation of CREB.
PG  - 197-206
LID - 10.1093/intimm/dxab112 [doi]
AB  - Myeloid cells play a pivotal role in immune responses against bacterial and 
      fungal infection. Among innate immune receptors, C-type lectin receptors (CLRs) 
      can induce a wide spectrum of cytokines through immunoreceptor tyrosine-based 
      activation motifs (ITAMs)-mediated signaling pathways. Dendritic cells (DCs) 
      produce IL-10 through CLR stimulation; however, the regulatory mechanism of IL-10 
      expression has not been elucidated. In the current study, we report that calcium 
      (Ca2+) signaling-deficient DCs produced more IL-10 than wild-type DCs. 
      Mechanistically, Ca2+-dependent phosphatase calcineurin directly inactivates cAMP 
      response element-binding protein (CREB), a transcription factor of Il10 in DCs, 
      through dephosphorylating CREB at serine 133. In calcineurin-deficient DCs, CREB 
      was highly phosphorylated and increased its binding to the Il10 promoter. 
      Elimination of mitogen-activated protein kinase (MAPK) signaling that 
      phosphorylates CREB, deficiency of CREB, as well as deletion of a CREB-binding 
      site in the Il10 promoter could diminish IL-10 production in DCs. Our findings 
      identified a novel substrate of calcineurin as well as a mechanism through which 
      Ca2+ signaling regulates IL-10 expression downstream of CLRs. As IL-10 is a 
      crucial immunosuppressive cytokine, this mechanism may counteract the 
      over-activated IL-10-producing signals induced by CARD9 and MAPK pathways, 
      preventing the ineffectiveness of the immune system during bacterial and fungal 
      infection.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of The 
      Japanese Society for Immunology. All rights reserved. For permissions, please 
      e-mail: journals.permissions@oup.com.
FAU - Lu, Xiuyuan
AU  - Lu X
AUID- ORCID: 0000-0002-0784-2871
AD  - Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka 
      University, Suita, Japan.
FAU - Oh-Hora, Masatsugu
AU  - Oh-Hora M
AD  - Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka 
      University, Suita, Japan.
AD  - Department of Biochemistry, Juntendo University School of Medicine, Tokyo, Japan.
FAU - Takeda, Kiyoshi
AU  - Takeda K
AD  - Laboratory of Immune Regulation, Department of Microbiology and Immunology, 
      Graduate School of Medicine, Osaka University, Suita, Japan.
AD  - Department of Mucosal Immunology, Immunology Frontier Research Center, Osaka 
      University, Suita, Japan.
AD  - Center for Infectious Disease Education and Research (CiDER), Osaka University, 
      Suita, Japan.
FAU - Yamasaki, Sho
AU  - Yamasaki S
AD  - Laboratory of Molecular Immunology, Immunology Frontier Research Center, Osaka 
      University, Suita, Japan.
AD  - Center for Infectious Disease Education and Research (CiDER), Osaka University, 
      Suita, Japan.
AD  - Department of Molecular Immunology, Research Institute for Microbial Diseases, 
      Osaka University, Suita, Japan.
AD  - Division of Molecular Design, Research Center for Systems Immunology, Medical 
      Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
AD  - Division of Molecular Immunology, Medical Mycology Research Center, Chiba 
      University, Chiba, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Cytokines)
RN  - 0 (Lectins, C-Type)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 3.1.3.16 (Calcineurin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcineurin/metabolism
MH  - Calcium/metabolism
MH  - *Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Cytokines/metabolism
MH  - Dendritic Cells
MH  - *Interleukin-10
MH  - Lectins, C-Type
MH  - Phosphorylation
OTO - NOTNLM
OT  - C-type lectin receptors (CLRs)
OT  - Ca2+ signaling
OT  - immune regulation
OT  - myeloid cells
OT  - phosphatase
EDAT- 2021/12/26 06:00
MHDA- 2022/05/07 06:00
CRDT- 2021/12/25 17:02
PHST- 2021/11/26 00:00 [received]
PHST- 2021/12/24 00:00 [accepted]
PHST- 2021/12/26 06:00 [pubmed]
PHST- 2022/05/07 06:00 [medline]
PHST- 2021/12/25 17:02 [entrez]
AID - 6483060 [pii]
AID - 10.1093/intimm/dxab112 [doi]
PST - ppublish
SO  - Int Immunol. 2022 Mar 25;34(4):197-206. doi: 10.1093/intimm/dxab112.