PMID- 19783688
OWN - NLM
STAT- MEDLINE
DCOM- 20091110
LR  - 20220318
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 183
IP  - 8
DP  - 2009 Oct 15
TI  - IFN-beta inhibits human Th17 cell differentiation.
PG  - 5418-27
LID - 10.4049/jimmunol.0803227 [doi]
AB  - IFN-beta-1a has been used over the past 15 years as a primary therapy for 
      relapsing-remitting multiple sclerosis (MS). However, the immunomodulatory 
      mechanisms that provide a therapeutic effect against this CNS inflammatory 
      disease are not yet completely elucidated. The effect of IFN-beta-1a on Th17 
      cells, which play a critical role in the development of the autoimmune response, 
      has not been extensively studied in humans. We have investigated the effect of 
      IFN-beta-1a on dendritic cells (DCs) and naive CD4(+)CD45RA(+) T cells derived 
      from untreated MS patients and healthy controls in the context of Th17 cell 
      differentiation. We report that IFN-beta-1a treatment down-regulated the 
      expression of IL-1beta and IL-23p19 in DCs, whereas it induced the gene 
      expression of IL-12p35 and IL-27p28. We propose that IFN-beta-1a-mediated 
      up-regulation of the suppressor of cytokine signaling 3 expression, induced via 
      STAT3 phosphorylation, mediates IL-1beta and IL-23 down-regulation, while 
      IFN-beta-1a-induced STAT1 phosphorylation induces IL-27p28 expression. 
      CD4(+)CD45RA(+) naive T cells cocultured with supernatants from 
      IFN-beta-1a-treated DCs exhibited decreased gene expression of the Th17 cell 
      markers retinoic acid-related orphan nuclear hormone receptor c (RORc), IL-17A, 
      and IL-23R. A direct IFN-beta-1a treatment of CD45RA(+) T cells cultured in 
      Th17-polarizing conditions also down-regulated RORc, IL-17A, and IL-23R, but 
      up-regulated IL-10 gene expression. Studies of the mechanisms involved in the 
      Th17 cell differentiation suggest that IFN-beta-1a inhibits IL-17 and induces 
      IL-10 secretion via activated STAT1 and STAT3, respectively. IFN-beta's 
      suppression of Th17 cell differentiation may represent its most relevant 
      mechanism of selective suppression of the autoimmune response in MS.
FAU - Ramgolam, Vinod S
AU  - Ramgolam VS
AD  - Department of Neurology, University of North Carolina at Chapel Hill, Chapel 
      Hill, NC 27599, USA.
FAU - Sha, Yonggang
AU  - Sha Y
FAU - Jin, Jianping
AU  - Jin J
FAU - Zhang, Xin
AU  - Zhang X
FAU - Markovic-Plese, Silva
AU  - Markovic-Plese S
LA  - eng
GR  - K08 NS045871/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 - 20090925
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (CCR6 protein, human)
RN  - 0 (IL23R protein, human)
RN  - 0 (Interleukin-12 Subunit p35)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-23 Subunit p19)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
RN  - 0 (RORC protein, human)
RN  - 0 (Receptors, CCR6)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT1 protein, human)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 130068-27-8 (Interleukin-10)
RN  - 77238-31-4 (Interferon-beta)
RN  - XRO4566Q4R (Interferon beta-1a)
SB  - IM
MH  - CD4-Positive T-Lymphocytes/drug effects/immunology
MH  - Cell Differentiation/*drug effects/immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/*drug effects/immunology
MH  - Down-Regulation/drug effects/immunology
MH  - Humans
MH  - Interferon beta-1a
MH  - Interferon-beta/*pharmacology
MH  - Interleukin-10/agonists/immunology/metabolism
MH  - Interleukin-12 Subunit p35/agonists/immunology/metabolism
MH  - Interleukin-17/*immunology
MH  - Interleukin-1beta/antagonists & inhibitors/immunology/metabolism
MH  - Interleukin-23 Subunit p19/antagonists & inhibitors/immunology/metabolism
MH  - Multiple Sclerosis/*immunology
MH  - Nuclear Receptor Subfamily 1, Group F, Member 3
MH  - Phosphorylation/drug effects/immunology
MH  - Receptors, CCR6/antagonists & inhibitors/immunology/metabolism
MH  - Receptors, Interleukin/antagonists & inhibitors/immunology/metabolism
MH  - Receptors, Retinoic Acid/immunology/metabolism
MH  - Receptors, Thyroid Hormone/immunology/metabolism
MH  - STAT1 Transcription Factor/drug effects/immunology/metabolism
MH  - STAT3 Transcription Factor/drug effects/immunology/metabolism
MH  - T-Lymphocytes, Helper-Inducer/*drug effects/immunology
MH  - Up-Regulation/drug effects/immunology
EDAT- 2009/09/29 06:00
MHDA- 2009/11/11 06:00
CRDT- 2009/09/29 06:00
PHST- 2009/09/29 06:00 [entrez]
PHST- 2009/09/29 06:00 [pubmed]
PHST- 2009/11/11 06:00 [medline]
AID - jimmunol.0803227 [pii]
AID - 10.4049/jimmunol.0803227 [doi]
PST - ppublish
SO  - J Immunol. 2009 Oct 15;183(8):5418-27. doi: 10.4049/jimmunol.0803227. Epub 2009 
      Sep 25.