PMID- 24706909
OWN - NLM
STAT- MEDLINE
DCOM- 20140616
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 111
IP  - 14
DP  - 2014 Apr 8
TI  - T cells down-regulate macrophage TNF production by IRAK1-mediated IL-10 
      expression and control innate hyperinflammation.
PG  - 5295-300
LID - 10.1073/pnas.1321427111 [doi]
AB  - Endotoxemia is caused by excessive inflammation, but the immune system has 
      various mechanisms to avoid collateral organ damage in endotoxemia. A handful of 
      reports have shown that innate immune responses are suppressed by the adaptive 
      immune system. However, the molecular mechanism by which adaptive immune cells 
      suppress innate inflammatory responses is not clear. Here, we report that T cells 
      are shown to interact with macrophages at the early stage of enodotoxemia and to 
      prolong survival of mice through controlling TNF and IL-10 levels by macrophage 
      CD40 stimulation. The cross-talk between CD40 and toll-like receptor (TLR4) 
      signaling first mediates IL-1 receptor-associated kinase 1 (IRAK1) nuclear 
      translocation and its binding to the IL-10 gene promoter in macrophages, without 
      interfering with the NFkappaB pathway. IL-10 is then detected by macrophages in an 
      autocrine fashion to destabilize Tnfa mRNA. To induce IRAK1-mediated IL-10 
      expression, signals from both CD40 and TLR4 are essential. CD40 signaling induces 
      IRAK1 sumoylation in the presence of TNF receptor-associated factor 2 (TRAF2) and 
      intracellular isoform of osteopontin (iOPN) whereas TLR4 signaling provides IFN 
      regulatory factor 5 (IRF5) as a chaperone for sumoylated IRAK1 nuclear 
      translocation. Interaction of T cells with macrophages was observed in the spleen 
      in vivo after endotoxemia induction with LPS injection. Our study demonstrates a 
      mechanistic basis for the immunosuppressive role of macrophage CD40 in LPS 
      endotoxemia.
FAU - Inoue, Makoto
AU  - Inoue M
AD  - Department of Immunology, Department of Medicine, Division of Infectious 
      Diseases, and Department of Molecular Genetics and Microbiology, Duke University 
      School of Medicine, Durham, NC 27710.
FAU - Arikawa, Tomohiro
AU  - Arikawa T
FAU - Chen, Yu-Hsun
AU  - Chen YH
FAU - Moriwaki, Yasuhiro
AU  - Moriwaki Y
FAU - Price, Michael
AU  - Price M
FAU - Brown, Michael
AU  - Brown M
FAU - Perfect, John R
AU  - Perfect JR
FAU - Shinohara, Mari L
AU  - Shinohara ML
LA  - eng
GR  - R01 AI073896/AI/NIAID NIH HHS/United States
GR  - R01AI073896/AI/NIAID NIH HHS/United States
GR  - R01 AI088100/AI/NIAID NIH HHS/United States
GR  - R21 AI103584/AI/NIAID NIH HHS/United States
GR  - R21AI103584/AI/NIAID NIH HHS/United States
GR  - P30 CA014236/CA/NCI NIH HHS/United States
GR  - R01AI088100/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140321
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antigens, CD)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases)
RN  - EC 2.7.11.1 (Irak1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Antigens, CD/immunology
MH  - Cell Nucleus/metabolism
MH  - *Down-Regulation
MH  - Inflammation/*immunology
MH  - Interleukin-1 Receptor-Associated Kinases/*physiology
MH  - Interleukin-10/*physiology
MH  - Macrophages/*immunology
MH  - Mice
MH  - Protein Transport
MH  - Signal Transduction
MH  - Sumoylation
MH  - T-Lymphocytes/*immunology
MH  - Toll-Like Receptor 4/metabolism
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
PMC - PMC3986140
OTO - NOTNLM
OT  - CD154
OT  - CD40L
OT  - OPN
OT  - T cell migration
OT  - simultaneous stimulation
COIS- The authors declare no conflict of interest.
EDAT- 2014/04/08 06:00
MHDA- 2014/06/17 06:00
PMCR- 2014/10/08
CRDT- 2014/04/08 06:00
PHST- 2014/04/08 06:00 [entrez]
PHST- 2014/04/08 06:00 [pubmed]
PHST- 2014/06/17 06:00 [medline]
PHST- 2014/10/08 00:00 [pmc-release]
AID - 1321427111 [pii]
AID - 201321427 [pii]
AID - 10.1073/pnas.1321427111 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5295-300. doi: 
      10.1073/pnas.1321427111. Epub 2014 Mar 21.