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Role of Blimp-1 in programing Th effector cells into IL-10 producers

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Role of Blimp-1 in programing Th effector cells into IL-10 producers. / Neumann, Christian; Heinrich, Frederik; Neumann, Katrin; Junghans, Victoria; Mashreghi, Mir-Farzin; Ahlers, Jonas; Janke, Marko; Rudolph, Christine; Mockel-Tenbrinck, Nadine; Kühl, Anja A; Heimesaat, Markus M; Esser, Charlotte; Im, Sin-Hyeog; Radbruch, Andreas; Rutz, Sascha; Scheffold, Alexander.

in: J EXP MED, Jahrgang 211, Nr. 9, 25.08.2014, S. 1807-19.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Neumann, C, Heinrich, F, Neumann, K, Junghans, V, Mashreghi, M-F, Ahlers, J, Janke, M, Rudolph, C, Mockel-Tenbrinck, N, Kühl, AA, Heimesaat, MM, Esser, C, Im, S-H, Radbruch, A, Rutz, S & Scheffold, A 2014, 'Role of Blimp-1 in programing Th effector cells into IL-10 producers', J EXP MED, Jg. 211, Nr. 9, S. 1807-19. https://doi.org/10.1084/jem.20131548

APA

Neumann, C., Heinrich, F., Neumann, K., Junghans, V., Mashreghi, M-F., Ahlers, J., Janke, M., Rudolph, C., Mockel-Tenbrinck, N., Kühl, A. A., Heimesaat, M. M., Esser, C., Im, S-H., Radbruch, A., Rutz, S., & Scheffold, A. (2014). Role of Blimp-1 in programing Th effector cells into IL-10 producers. J EXP MED, 211(9), 1807-19. https://doi.org/10.1084/jem.20131548

Vancouver

Neumann C, Heinrich F, Neumann K, Junghans V, Mashreghi M-F, Ahlers J et al. Role of Blimp-1 in programing Th effector cells into IL-10 producers. J EXP MED. 2014 Aug 25;211(9):1807-19. https://doi.org/10.1084/jem.20131548

Bibtex

@article{bd7864fca08443b6a417a1d7a353a8f8,
title = "Role of Blimp-1 in programing Th effector cells into IL-10 producers",
abstract = "Secretion of the immunosuppressive cytokine interleukin (IL) 10 by effector T cells is an essential mechanism of self-limitation during infection. However, the transcriptional regulation of IL-10 expression in proinflammatory T helper (Th) 1 cells is insufficiently understood. We report a crucial role for the transcriptional regulator Blimp-1, induced by IL-12 in a STAT4-dependent manner, in controlling IL-10 expression in Th1 cells. Blimp-1 deficiency led to excessive inflammation during Toxoplasma gondii infection with increased mortality. IL-10 production from Th1 cells was strictly dependent on Blimp-1 but was further enhanced by the synergistic function of c-Maf, a transcriptional regulator of IL-10 induced by multiple factors, such as the Notch pathway. We found Blimp-1 expression, which was also broadly induced by IL-27 in effector T cells, to be antagonized by transforming growth factor (TGF) β. While effectively blocking IL-10 production from Th1 cells, TGF-β shifted IL-10 regulation from a Blimp-1-dependent to a Blimp-1-independent pathway in IL-27-induced Tr1 (T regulatory 1) cells. Our findings further illustrate how IL-10 regulation in Th cells relies on several transcriptional programs that integrate various signals from the environment to fine-tune expression of this critical immunosuppressive cytokine.",
keywords = "Animals, Interleukin-10, Interleukin-12, Interleukins, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Proto-Oncogene Proteins c-maf, Receptors, Notch, STAT4 Transcription Factor, Signal Transduction, Th1 Cells, Toxoplasmosis, Transcription Factors, Transforming Growth Factor beta",
author = "Christian Neumann and Frederik Heinrich and Katrin Neumann and Victoria Junghans and Mir-Farzin Mashreghi and Jonas Ahlers and Marko Janke and Christine Rudolph and Nadine Mockel-Tenbrinck and K{\"u}hl, {Anja A} and Heimesaat, {Markus M} and Charlotte Esser and Sin-Hyeog Im and Andreas Radbruch and Sascha Rutz and Alexander Scheffold",
note = "{\textcopyright} 2014 Neumann et al.",
year = "2014",
month = aug,
day = "25",
doi = "10.1084/jem.20131548",
language = "English",
volume = "211",
pages = "1807--19",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "9",

}

RIS

TY - JOUR

T1 - Role of Blimp-1 in programing Th effector cells into IL-10 producers

AU - Neumann, Christian

AU - Heinrich, Frederik

AU - Neumann, Katrin

AU - Junghans, Victoria

AU - Mashreghi, Mir-Farzin

AU - Ahlers, Jonas

AU - Janke, Marko

AU - Rudolph, Christine

AU - Mockel-Tenbrinck, Nadine

AU - Kühl, Anja A

AU - Heimesaat, Markus M

AU - Esser, Charlotte

AU - Im, Sin-Hyeog

AU - Radbruch, Andreas

AU - Rutz, Sascha

AU - Scheffold, Alexander

N1 - © 2014 Neumann et al.

PY - 2014/8/25

Y1 - 2014/8/25

N2 - Secretion of the immunosuppressive cytokine interleukin (IL) 10 by effector T cells is an essential mechanism of self-limitation during infection. However, the transcriptional regulation of IL-10 expression in proinflammatory T helper (Th) 1 cells is insufficiently understood. We report a crucial role for the transcriptional regulator Blimp-1, induced by IL-12 in a STAT4-dependent manner, in controlling IL-10 expression in Th1 cells. Blimp-1 deficiency led to excessive inflammation during Toxoplasma gondii infection with increased mortality. IL-10 production from Th1 cells was strictly dependent on Blimp-1 but was further enhanced by the synergistic function of c-Maf, a transcriptional regulator of IL-10 induced by multiple factors, such as the Notch pathway. We found Blimp-1 expression, which was also broadly induced by IL-27 in effector T cells, to be antagonized by transforming growth factor (TGF) β. While effectively blocking IL-10 production from Th1 cells, TGF-β shifted IL-10 regulation from a Blimp-1-dependent to a Blimp-1-independent pathway in IL-27-induced Tr1 (T regulatory 1) cells. Our findings further illustrate how IL-10 regulation in Th cells relies on several transcriptional programs that integrate various signals from the environment to fine-tune expression of this critical immunosuppressive cytokine.

AB - Secretion of the immunosuppressive cytokine interleukin (IL) 10 by effector T cells is an essential mechanism of self-limitation during infection. However, the transcriptional regulation of IL-10 expression in proinflammatory T helper (Th) 1 cells is insufficiently understood. We report a crucial role for the transcriptional regulator Blimp-1, induced by IL-12 in a STAT4-dependent manner, in controlling IL-10 expression in Th1 cells. Blimp-1 deficiency led to excessive inflammation during Toxoplasma gondii infection with increased mortality. IL-10 production from Th1 cells was strictly dependent on Blimp-1 but was further enhanced by the synergistic function of c-Maf, a transcriptional regulator of IL-10 induced by multiple factors, such as the Notch pathway. We found Blimp-1 expression, which was also broadly induced by IL-27 in effector T cells, to be antagonized by transforming growth factor (TGF) β. While effectively blocking IL-10 production from Th1 cells, TGF-β shifted IL-10 regulation from a Blimp-1-dependent to a Blimp-1-independent pathway in IL-27-induced Tr1 (T regulatory 1) cells. Our findings further illustrate how IL-10 regulation in Th cells relies on several transcriptional programs that integrate various signals from the environment to fine-tune expression of this critical immunosuppressive cytokine.

KW - Animals

KW - Interleukin-10

KW - Interleukin-12

KW - Interleukins

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mice, Transgenic

KW - Proto-Oncogene Proteins c-maf

KW - Receptors, Notch

KW - STAT4 Transcription Factor

KW - Signal Transduction

KW - Th1 Cells

KW - Toxoplasmosis

KW - Transcription Factors

KW - Transforming Growth Factor beta

U2 - 10.1084/jem.20131548

DO - 10.1084/jem.20131548

M3 - SCORING: Journal article

C2 - 25073792

VL - 211

SP - 1807

EP - 1819

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 9

ER -