PMID- 21516112
OWN - NLM
STAT- MEDLINE
DCOM- 20110722
LR  - 20220223
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Linking)
VI  - 12
IP  - 6
DP  - 2011 Jun
TI  - RORgammat drives production of the cytokine GM-CSF in helper T cells, which is 
      essential for the effector phase of autoimmune neuroinflammation.
PG  - 560-7
LID - 10.1038/ni.2027 [doi]
AB  - Although the role of the T(H)1 and T(H)17 subsets of helper T cells as disease 
      mediators in autoimmune neuroinflammation remains a subject of some debate, none 
      of their signature cytokines are essential for disease development. Here we 
      report that interleukin 23 (IL-23) and the transcription factor RORgammat drove 
      expression of the cytokine GM-CSF in helper T cells, whereas IL-12, interferon-gamma 
      (IFN-gamma) and IL-27 acted as negative regulators. Autoreactive helper T cells 
      specifically lacking GM-CSF failed to initiate neuroinflammation despite 
      expression of IL-17A or IFN-gamma, whereas GM-CSF secretion by Ifng(-/-)Il17a(-/-) 
      helper T cells was sufficient to induce experimental autoimmune encephalomyelitis 
      (EAE). During the disease effector phase, GM-CSF sustained neuroinflammation via 
      myeloid cells that infiltrated the central nervous system. Thus, in contrast to 
      all other known helper T cell-derived cytokines, GM-CSF serves a nonredundant 
      function in the initiation of autoimmune inflammation regardless of helper T cell 
      polarization.
FAU - Codarri, Laura
AU  - Codarri L
AD  - Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
FAU - Gyulveszi, Gabor
AU  - Gyulveszi G
FAU - Tosevski, Vinko
AU  - Tosevski V
FAU - Hesske, Lysann
AU  - Hesske L
FAU - Fontana, Adriano
AU  - Fontana A
FAU - Magnenat, Laurent
AU  - Magnenat L
FAU - Suter, Tobias
AU  - Suter T
FAU - Becher, Burkhard
AU  - Becher B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110424
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Glycoproteins)
RN  - 0 (Il27 protein, mouse)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-23)
RN  - 0 (Interleukins)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
RN  - 0 (Peptide Fragments)
RN  - 0 (myelin oligodendrocyte glycoprotein (35-55))
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
CIN - Nat Immunol. 2011 Jun;12(6):521-2. doi: 10.1038/ni.2044. PMID: 21587311
CIN - Nat Rev Immunol. 2011 Jun;11(6):370-1. doi: 10.1038/nri2996. PMID: 21597474
MH  - Animals
MH  - Cells, Cultured
MH  - Encephalomyelitis, Autoimmune, Experimental/chemically 
      induced/immunology/*metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Glycoproteins
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/genetics/immunology/*metabolism
MH  - Interferon-gamma/genetics/immunology/pharmacology
MH  - Interleukin-12/pharmacology
MH  - Interleukin-17/genetics/immunology
MH  - Interleukin-23/pharmacology
MH  - Interleukins/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Myelin-Oligodendrocyte Glycoprotein
MH  - Nuclear Receptor Subfamily 1, Group F, Member 3/genetics/immunology/*metabolism
MH  - Peptide Fragments
MH  - T-Lymphocytes, Helper-Inducer/immunology/*metabolism
MH  - Th1 Cells/drug effects/immunology/metabolism
MH  - Th17 Cells/drug effects/immunology/metabolism
EDAT- 2011/04/26 06:00
MHDA- 2011/07/23 06:00
CRDT- 2011/04/26 06:00
PHST- 2010/11/10 00:00 [received]
PHST- 2011/03/23 00:00 [accepted]
PHST- 2011/04/26 06:00 [entrez]
PHST- 2011/04/26 06:00 [pubmed]
PHST- 2011/07/23 06:00 [medline]
AID - ni.2027 [pii]
AID - 10.1038/ni.2027 [doi]
PST - ppublish
SO  - Nat Immunol. 2011 Jun;12(6):560-7. doi: 10.1038/ni.2027. Epub 2011 Apr 24.