IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation

The Journal of Experimental Medicine
Chih-Chung LinBrian T Edelson

Abstract

The features that define autoreactive T helper (Th) cell pathogenicity remain obscure. We have previously shown that Th cells require the transcription factor Bhlhe40 to mediate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Here, using Bhlhe40 reporter mice and analyzing both polyclonal and TCR transgenic Th cells, we found that Bhlhe40 expression was heterogeneous after EAE induction, with Bhlhe40-expressing cells displaying marked production of IFN-γ, IL-17A, and granulocyte-macrophage colony-stimulating factor. In adoptive transfer EAE models, Bhlhe40-deficient Th1 and Th17 cells were both nonencephalitogenic. Pertussis toxin (PTX), a classical co-adjuvant for actively induced EAE, promoted IL-1β production by myeloid cells in the draining lymph node and served as a strong stimulus for Bhlhe40 expression in Th cells. Furthermore, PTX co-adjuvanticity was Bhlhe40 dependent. IL-1β induced Bhlhe40 expression in polarized Th17 cells, and Bhlhe40-expressing cells exhibited an encephalitogenic transcriptional signature. In vivo, IL-1R signaling was required for full Bhlhe40 expression by Th cells after immunization. Overall, we demonstrate that Bhlhe40 expression identifies encephalitogenic ...Continue Reading

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Citations

Jun 7, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chih-Chung Lin, Brian T Edelson
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Datasets Mentioned

BETA
GSE15907
GSE37448
GM-CSF
GSE23505
GSE75407

Methods Mentioned

BETA
transgenic
flow cytometry
PCR
FACS
PMA

Software Mentioned

QCapture
Prism
FlowJo
GENE
GraphPad
ImageJ
Arraystar
Immgen

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