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PMID: 19234160 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

IL-17 signaling-independent central nervous system autoimmunity is negatively regulated by TGF-beta.

Journal of immunology (Baltimore, Md. : 1950) ·Vol. 182 ·No. 5 ·2009-03-01 ·Pages 2665-71

Gonzalez-García I, Zhao Y, Ju S, Gu Q, Liu L, Kolls JK, Lu B

Abstract

Recent studies have established an important role of Th17 in induction of autoimmune diseases. We have found that although IL-17 receptor A (IL-17RA)(-/-) mice were resistant to experimental autoimmune encephalomyelitis, a small number of them developed milder clinical signs of this autoimmune disease. In addition, blockade of TGF-beta in IL-17RA(-/-) mice resulted in much more severe clinical signs of experimental autoimmune encephalomyelitis and significantly increased parenchymal lymphocyte infiltration in the CNS. Furthermore, the number of autoreactive Th1 cells was greatly increased in the inflamed spinal cord of IL-17RA(-/-) mice. These data support a role of IL-17RA-independent mechanisms in causing autoimmunity and its regulation by TGF-beta.

MeSH Terms
Amino Acid Sequence Animals Central Nervous System/immunology,metabolism,pathology Down-Regulation/genetics,immunology Encephalomyelitis, Autoimmune, Experimental/immunology,metabolism,pathology Inflammation Mediators/antagonists & inhibitors,physiology Interleukin-17/deficiency,genetics,physiology Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data Receptors, Interleukin-17/deficiency,genetics,physiology Severity of Illness Index Signal Transduction/genetics,immunology Th1 Cells/immunology,metabolism,pathology Transforming Growth Factor beta/antagonists & inhibitors,physiology
Chemicals
Inflammation Mediators Interleukin-17 Receptors, Interleukin-17 Transforming Growth Factor beta
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Gonzalez-García Ines
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Zhao Yani
Ju Songguang
Gu Qin
Liu Lin
Kolls Jay K
Lu Binfeng
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Article Info
Journal
Journal of immunology (Baltimore, Md. : 1950)
Abbr.
J Immunol
ISSN
1550-6606
DOI
10.4049/jimmunol.0802221
Published
2009-03-01
Pages
2665-71
Language
English
Region
United States
NLM ID
2985117R
PMCID
PMC2800821
Subset
IM
Grants
NIAID NIH HHS · R01 AI063496-01A1 · United States
NIAMS NIH HHS · 1 K01 AR048854 · United States
NIAMS NIH HHS · P30-AR47372 · United States
NIAID NIH HHS · R01 AI063496-04 · United States
NIAMS NIH HHS · P30 AR047372 · United States
NIAID NIH HHS · R01 AI063496-02 · United States
NIAID NIH HHS · AI063496 · United States
NIAMS NIH HHS · K01 AR048854 · United States
NIAID NIH HHS · R01 AI063496 · United States
NIAID NIH HHS · R01 AI063496-03 · United States
External Links
PubMed source DOI: 10.4049/jimmunol.0802221 PMC Full Text View journal details
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