@article{022ff37cc28141ed9e10b7fbeacf8948,
title = "Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation",
abstract = "T H 1 and T H 17 cells mediate neuroinflammation in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Pathogenic T H cells in EAE must produce the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). T H cell pathogenicity in EAE is also regulated by cell-intrinsic production of the immunosuppressive cytokine interleukin 10 (IL-10). Here we demonstrate that mice deficient for the basic helix-loop-helix (bHLH) transcription factor Bhlhe40 (Bhlhe40 -/-) are resistant to the induction of EAE. Bhlhe40 is required in vivo in a T cell-intrinsic manner, where it positively regulates the production of GM-CSF and negatively regulates the production of IL-10. In vitro, GM-CSF secretion is selectively abrogated in polarized Bhlhe40 -/- T H 1 and T H 17 cells, and these cells show increased production of IL-10. Blockade of IL-10 receptor in Bhlhe40 -/- mice renders them susceptible to EAE. These findings identify Bhlhe40 as a critical regulator of autoreactive T-cell pathogenicity.",
author = "Lin, {Chih Chung} and Bradstreet, {Tara R.} and Schwarzkopf, {Elizabeth A.} and Julia Sim and Carrero, {Javier A.} and Chun Chou and Cook, {Lindsey E.} and Takeshi Egawa and Reshma Taneja and Murphy, {Theresa L.} and Russell, {John H.} and Edelson, {Brian T.}",
note = "Funding Information: We thank Kenneth Murphy, Emil Unanue and Edward Pearce for advice and reagents. This work was supported by a Burroughs Wellcome Fund Career Award for Medical Scientists, an American Society of Hematology Scholar Award and an Edward Mal-linckrodt Jr Foundation Grant to B.T.E. This investigation was also supported in part by a grant from the National Multiple Sclerosis Society (4352A61) to J.H.R. C.-C.L. was supported by the McDonnell International Scholars Academy at Washington University. Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.",
year = "2014",
month = apr,
day = "3",
doi = "10.1038/ncomms4551",
language = "English",
volume = "5",
journal = "Nature communications",
issn = "2041-1723",
}