Monday, 21 April 2014

Controlling T cell function

Lin CC, Bradstreet TR, Schwarzkopf EA, Sim J, Carrero JA, Chou C, Cook LE, Egawa T, Taneja R, Murphy TL, Russell JH, Edelson BT. Bhlhe40 controls cytokine production by T cells and is essential for pathogenicity in autoimmune neuroinflammation. Nat Commun. 2014 Apr 3;5:3551. doi: 10.1038/ncomms4551.



TH1 and TH17 cells mediate neuroinflammation in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Pathogenic TH cells in EAE must produce the pro-inflammatory cytokine granulocyte-macrophage colony stimulating factor (GM-CSF). TH 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(-/-) TH1 and TH17 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.
Granulocyte-macrophage colony-stimulating factor (GM-CSF is a protein secreted by macrophages, T cells, mast cells, NK cells, endothelial cells and fibroblasts and interleukin-ten is a cytokine that can regulate T cell function, incluing that activated via the basic helix loop transcription factor. However, Interelukin ten is also a B cell growth factor. So would it succeed or fail in MS?

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