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

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Title
Role of Blimp-1 in programing Th effector cells into IL-10 producers
Author(s)
Neumann, C; Heinrich, F; Neumann, K; Junghans, V; Mashreghi, MF; Ahlers, J; Janke, M; Rudolph, C; Mockel-Tenbrinck, N; Kuhl, AA; Heimesaat, MM; Esser, C; Sin Hyeog Im; Radbruch, A; Rutz, S; Scheffold, A
Publication Date
2014-08
Journal
JOURNAL OF EXPERIMENTAL MEDICINE, v.211, no.9, pp.1807 - 1819
Publisher
ROCKEFELLER UNIV PRESS
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) . While effectively blocking IL-10 production from Th1 cells, TGF- 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.
URI
http://pr.ibs.re.kr/handle/8788114/933
DOI
10.1084/jem.20131548
ISSN
0022-1007
Appears in Collections:
Academy of Immunology and Microbiology(면역 미생물 공생 연구단) > Journal Papers (저널논문)
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