IFNγ suppresses the expression of GFI1 and thereby inhibits Th2 cell proliferation

While IFNγ is a well-known cytokine that actively promotes the type I immune response, it is also known to suppress the type II response by inhibiting the differentiation and proliferation of Th2 cells. However, the mechanism by which IFNγ suppresses Th2 cell proliferation is still not fully underst...

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Published inPloS one Vol. 16; no. 11; p. e0260204
Main Authors Sarkar, Murshed H, Yagi, Ryoji, Endo, Yukihiro, Koyama-Nasu, Ryo, Wang, Yangsong, Hasegawa, Ichita, Ito, Toshihiro, Junttila, Ilkka S, Zhu, Jinfang, Kimura, Motoko Y, Nakayama, Toshinori
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 22.11.2021
Public Library of Science (PLoS)
Subjects
Animals
Antigens
Apoptosis
Biology and Life Sciences
Cell Cycle
Cell differentiation
Cell growth
Cell Proliferation
Cells, Cultured
Clonal deletion
Cloning
Cytokines
DNA-Binding Proteins - genetics
Down-Regulation
Engineering and Technology
Gene Deletion
Gene expression
Growth factors
Helper cells
Immune response
Immunology
Interferon-gamma - immunology
Laboratories
Lymphocytes
Lymphocytes T
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Research and Analysis Methods
T cell receptors
Th2 Cells - cytology
Th2 Cells - immunology
Th2 Cells - metabolism
Transcription Factors - genetics
γ-Interferon
Japan
Finland
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Summary:While IFNγ is a well-known cytokine that actively promotes the type I immune response, it is also known to suppress the type II response by inhibiting the differentiation and proliferation of Th2 cells. However, the mechanism by which IFNγ suppresses Th2 cell proliferation is still not fully understood. We found that IFNγ decreases the expression of growth factor independent-1 transcriptional repressor (GFI1) in Th2 cells, resulting in the inhibition of Th2 cell proliferation. The deletion of the Gfi1 gene in Th2 cells results in the failure of their proliferation, accompanied by an impaired cell cycle progression. In contrast, the enforced expression of GFI1 restores the defective Th2 cell proliferation, even in the presence of IFNγ. These results demonstrate that GFI1 is a key molecule in the IFNγ-mediated inhibition of Th2 cell proliferation.
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Competing Interests: The authors declare no conflicts of interest in association with the present study.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0260204