PMID- 20534530
OWN - NLM
STAT- MEDLINE
DCOM- 20100722
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 107
IP  - 25
DP  - 2010 Jun 22
TI  - Identification of an IL-27/osteopontin axis in dendritic cells and its modulation 
      by IFN-gamma limits IL-17-mediated autoimmune inflammation.
PG  - 11495-500
LID - 10.1073/pnas.1002099107 [doi]
AB  - Dendritic cells (DCs) play a central role in determining the induction of T cell 
      responses. IL-27 production by DCs favors induction of IL-10-producing regulatory 
      T cells, whereas osteopontin (OPN) promotes pathogenic IL-17 T cell responses. 
      The regulatory mechanisms in DCs that control these two cells types are not 
      understood well. Here, we show that IFN-gamma induces IL-27 while inhibiting OPN 
      expression in DCs both in vitro and in vivo and that engagement of IFN-gammaR 
      expressed by DCs leads to suppression of IL-17 production while inducing IL-10 
      from T cells. DCs modified by IFN-gamma acquire IL-27-dependent regulatory 
      function, promote IL-10-mediated T cell tolerance, and suppress autoimmune 
      inflammation. Thus, our results identify a previously unknown pathway by which 
      IFN-gamma limits IL-17-mediated autoimmune inflammation through differential 
      regulation of OPN and IL-27 expression in DCs.
FAU - Murugaiyan, Gopal
AU  - Murugaiyan G
AD  - Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical 
      School, Boston, MA 02115, USA.
FAU - Mittal, Akanksha
AU  - Mittal A
FAU - Weiner, Howard L
AU  - Weiner HL
LA  - eng
GR  - R01 AI043458/AI/NIAID NIH HHS/United States
GR  - NS23132/NS/NINDS NIH HHS/United States
GR  - NS038037/NS/NINDS NIH HHS/United States
GR  - F32AI075761/AI/NIAID NIH HHS/United States
GR  - F32 AI075761/AI/NIAID NIH HHS/United States
GR  - AI043458/AI/NIAID NIH HHS/United States
GR  - R01 NS023132/NS/NINDS NIH HHS/United States
GR  - P01 NS038037-10/NS/NINDS NIH HHS/United States
GR  - P01 NS038037/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100607
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 (Interleukin-17)
RN  - 0 (Peptides)
RN  - 106441-73-0 (Osteopontin)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - *Autoimmunity
MH  - CD4-Positive T-Lymphocytes/cytology
MH  - Coculture Techniques
MH  - Encephalomyelitis, Autoimmune, Experimental/*metabolism
MH  - Interferon-gamma/*metabolism
MH  - Interleukin-17/*metabolism
MH  - Mice
MH  - Models, Biological
MH  - Osteopontin/*metabolism
MH  - Peptides/chemistry
MH  - Phenotype
MH  - Spleen/cytology
MH  - Time Factors
PMC - PMC2895126
COIS- The authors declare no conflict of interest.
EDAT- 2010/06/11 06:00
MHDA- 2010/07/23 06:00
PMCR- 2010/12/22
CRDT- 2010/06/11 06:00
PHST- 2010/06/11 06:00 [entrez]
PHST- 2010/06/11 06:00 [pubmed]
PHST- 2010/07/23 06:00 [medline]
PHST- 2010/12/22 00:00 [pmc-release]
AID - 1002099107 [pii]
AID - 201002099 [pii]
AID - 10.1073/pnas.1002099107 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11495-500. doi: 
      10.1073/pnas.1002099107. Epub 2010 Jun 7.