Please use this identifier to cite or link to this item: https://doi.org/10.1084/jem.20150568
Title: IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation
Authors: Lin, Chih-Chung
Bradstreet, Tara R
Schwarzkopf, Elizabeth A
Jarjour, Nicholas N
Chou, Chun
Archambault, Angela S
Sim, Julia
Zinselmeyer, Bernd H
Carrero, Javier A
Wu, Gregory F
Taneja, Reshma 
Artyomov, Maxim N
Russell, John H
Edelson, Brian T
Keywords: T-Lymphocytes, Helper-Inducer
Animals
Mice, Inbred C57BL
Mice, Transgenic
Mice, Knockout
Mice
Encephalomyelitis, Autoimmune, Experimental
Pertussis Toxin
Homeodomain Proteins
Interleukin-10
Adjuvants, Immunologic
Cytokines
Adoptive Transfer
Signal Transduction
Gene Expression
Basic Helix-Loop-Helix Transcription Factors
Forkhead Transcription Factors
Interleukin-1beta
Receptors, Interleukin-1 Type I
Issue Date: 8-Feb-2016
Citation: Lin, Chih-Chung, Bradstreet, Tara R, Schwarzkopf, Elizabeth A, Jarjour, Nicholas N, Chou, Chun, Archambault, Angela S, Sim, Julia, Zinselmeyer, Bernd H, Carrero, Javier A, Wu, Gregory F, Taneja, Reshma, Artyomov, Maxim N, Russell, John H, Edelson, Brian T (2016-02-08). IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation. JOURNAL OF EXPERIMENTAL MEDICINE 213 (2) : 251-271. ScholarBank@NUS Repository. https://doi.org/10.1084/jem.20150568
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 Th cells and defines a PTX-IL-1-Bhlhe40 pathway active in EAE.
Source Title: JOURNAL OF EXPERIMENTAL MEDICINE
URI: https://scholarbank.nus.edu.sg/handle/10635/155228
ISSN: 00221007
15409538
DOI: 10.1084/jem.20150568
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