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

Author:

Sarkar Murshed H.,Yagi Ryoji,Endo Yukihiro,Koyama-Nasu Ryo,Wang Yangsong,Hasegawa Ichita,Ito Toshihiro,Junttila Ilkka S.,Zhu Jinfang,Kimura Motoko Y.ORCID,Nakayama Toshinori

Abstract

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.

Funder

Ministry of Education, Culture, Sports, Science and Technology

Kanae Foundation for the Promotion of Medical Science

Kashiwado Memorial Foundation

Hamaguchi Foundation for the Advancement of Biochemistry

Takeda Science Foundation

Academy of Finland

National Academy of Finland

Competitive State Research Financing of the Expert Responsibility Area of Fimlab Laboratories

Tampere University Hospital Support Foundation

Tampere Tuberculosis Foundation

Publisher

Public Library of Science (PLoS)

Subject

Multidisciplinary

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