Egr2-independent, Klf1-mediated induction of PD-L1 in CD4+ T cells

Abstract Programmed death ligand 1 (PD-L1)-mediated induction of immune tolerance has been vigorously investigated in autoimmunity and anti-tumor immunity. However, details of the mechanism by which PD-L1 is induced in CD4+ T cells are unknown. Here, we revealed the potential function of Klf1 and Eg...

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Autores principales:	Shuzo Teruya, Tomohisa Okamura, Toshihiko Komai, Mariko Inoue, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/789bd4f972e140fabb92cade1c6bfd4f
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spelling	oai:doaj.org-article:789bd4f972e140fabb92cade1c6bfd4f2021-12-02T15:08:43ZEgr2-independent, Klf1-mediated induction of PD-L1 in CD4+ T cells10.1038/s41598-018-25302-12045-2322https://doaj.org/article/789bd4f972e140fabb92cade1c6bfd4f2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25302-1https://doaj.org/toc/2045-2322Abstract Programmed death ligand 1 (PD-L1)-mediated induction of immune tolerance has been vigorously investigated in autoimmunity and anti-tumor immunity. However, details of the mechanism by which PD-L1 is induced in CD4+ T cells are unknown. Here, we revealed the potential function of Klf1 and Egr2-mediated induction of PD-L1 in CD4+ T cells. We focused on the molecules specifically expressed in CD4+CD25−LAG3+ regulatory T cells (LAG3+ Tregs) highly express of PD-L1 and transcription factor Egr2. Although ectopic expression of Egr2 induced PD-L1, a deficiency of Egr2 did not affect its expression, indicating the involvement of another PD-L1 induction mechanism. Comprehensive gene expression analysis of LAG3+ Tregs and in silico binding predictions revealed that Krüppel-like factor 1 (Klf1) is a candidate inducer of the PD-L1 gene (Cd274). Klf1 is a transcription factor that promotes β-globin synthesis in erythroid progenitors, and its role in immunological homeostasis is unknown. Ectopic expression of Klf1 induced PD-L1 in CD4+ T cells through activation of the PI3K-mTOR signaling pathway, independent of STATs signaling and Egr2 expression. Our findings indicate that Klf1 and Egr2 are modulators of PD-L1-mediated immune suppression in CD4+ T cells and might provide new insights into therapeutic targets for autoimmune diseases and malignancies.Shuzo TeruyaTomohisa OkamuraToshihiko KomaiMariko InoueYukiko IwasakiShuji SumitomoHirofumi ShodaKazuhiko YamamotoKeishi FujioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shuzo Teruya Tomohisa Okamura Toshihiko Komai Mariko Inoue Yukiko Iwasaki Shuji Sumitomo Hirofumi Shoda Kazuhiko Yamamoto Keishi Fujio Egr2-independent, Klf1-mediated induction of PD-L1 in CD4+ T cells
description	Abstract Programmed death ligand 1 (PD-L1)-mediated induction of immune tolerance has been vigorously investigated in autoimmunity and anti-tumor immunity. However, details of the mechanism by which PD-L1 is induced in CD4+ T cells are unknown. Here, we revealed the potential function of Klf1 and Egr2-mediated induction of PD-L1 in CD4+ T cells. We focused on the molecules specifically expressed in CD4+CD25−LAG3+ regulatory T cells (LAG3+ Tregs) highly express of PD-L1 and transcription factor Egr2. Although ectopic expression of Egr2 induced PD-L1, a deficiency of Egr2 did not affect its expression, indicating the involvement of another PD-L1 induction mechanism. Comprehensive gene expression analysis of LAG3+ Tregs and in silico binding predictions revealed that Krüppel-like factor 1 (Klf1) is a candidate inducer of the PD-L1 gene (Cd274). Klf1 is a transcription factor that promotes β-globin synthesis in erythroid progenitors, and its role in immunological homeostasis is unknown. Ectopic expression of Klf1 induced PD-L1 in CD4+ T cells through activation of the PI3K-mTOR signaling pathway, independent of STATs signaling and Egr2 expression. Our findings indicate that Klf1 and Egr2 are modulators of PD-L1-mediated immune suppression in CD4+ T cells and might provide new insights into therapeutic targets for autoimmune diseases and malignancies.
format	article
author	Shuzo Teruya Tomohisa Okamura Toshihiko Komai Mariko Inoue Yukiko Iwasaki Shuji Sumitomo Hirofumi Shoda Kazuhiko Yamamoto Keishi Fujio
author_facet	Shuzo Teruya Tomohisa Okamura Toshihiko Komai Mariko Inoue Yukiko Iwasaki Shuji Sumitomo Hirofumi Shoda Kazuhiko Yamamoto Keishi Fujio
author_sort	Shuzo Teruya
title	Egr2-independent, Klf1-mediated induction of PD-L1 in CD4+ T cells
title_short	Egr2-independent, Klf1-mediated induction of PD-L1 in CD4+ T cells
title_full	Egr2-independent, Klf1-mediated induction of PD-L1 in CD4+ T cells
title_fullStr	Egr2-independent, Klf1-mediated induction of PD-L1 in CD4+ T cells
title_full_unstemmed	Egr2-independent, Klf1-mediated induction of PD-L1 in CD4+ T cells
title_sort	egr2-independent, klf1-mediated induction of pd-l1 in cd4+ t cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/789bd4f972e140fabb92cade1c6bfd4f
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Egr2-independent, Klf1-mediated induction of PD-L1 in CD4+ T cells

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