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Highly polarized Th17 cells induce EAE via a T-bet independent mechanism.

Authors :
Grifka‐Walk, Heather M.
Lalor, Stephen J.
Segal, Benjamin M.
Source :
European Journal of Immunology; Nov2013, Vol. 43 Issue 11, p2824-2831, 8p
Publication Year :
2013

Abstract

In the MOG<subscript>35-55</subscript> induced EAE model, autoreactive Th17 cells that accumulate in the central nervous system acquire Th1 characteristics via a T-bet dependent mechanism. It remains to be determined whether Th17 plasticity and encephalitogenicity are causally related to each other. Here, we show that IL-23 polarized T-bet<superscript>−/−</superscript> Th17 cells are unimpaired in either activation or proliferation, and induce higher quantities of the chemokines RANTES and CXCL2 than WT Th17 cells. Unlike their WT counterparts, T-bet<superscript>−/−</superscript> Th17 cells retain an IL-17<superscript>hi</superscript> IFN-γ<superscript>neg-lo</superscript> cytokine profile following adoptive transfer into syngeneic hosts. This population of highly polarized Th17 effectors is capable of mediating EAE, albeit with a milder clinical course. It has previously been reported that the signature Th1 and Th17 effector cytokines, IFN-γ and IL-17, are dispensable for the development of autoimmune demyelinating disease. The current study demonstrates that the 'master regulator' transcription factor, T-bet, is also not universally required for encephalitogenicity. Our results contribute to a growing body of data showing heterogeneity of myelin-reactive T cells and the independent mechanisms they employ to inflict damage to central nervous system tissues, complicating the search for therapeutic targets relevant across the spectrum of individuals with multiple sclerosis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00142980
Volume :
43
Issue :
11
Database :
Complementary Index
Journal :
European Journal of Immunology
Publication Type :
Academic Journal
Accession number :
92038308
Full Text :
https://doi.org/10.1002/eji.201343723