Runx-mediated regulation of CCL5 via antagonizing two enhancers influences immune cell function and anti-tumor immunity

Wooseok Seo (), Kanako Shimizu, Satoshi Kojo, Arinze Okeke, Terumi Kohwi-Shigematsu, Shin-ichiro Fujii and Ichiro Taniuchi ()
Additional contact information
Wooseok Seo: Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences
Kanako Shimizu: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences
Satoshi Kojo: Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences
Arinze Okeke: Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences
Terumi Kohwi-Shigematsu: University of California
Shin-ichiro Fujii: Laboratory for Immunotherapy, RIKEN Center for Integrative Medical Sciences
Ichiro Taniuchi: Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract CCL5 is a unique chemokine with distinct stage and cell-type specificities for regulating inflammation, but how these specificities are achieved and how CCL5 modulates immune responses is not well understood. Here we identify two stage-specific enhancers: the proximal enhancer mediates the constitutive CCL5 expression during the steady state, while the distal enhancer located 1.35 Mb from the promoter induces CCL5 expression in activated cells. Both enhancers are antagonized by RUNX/CBFβ complexes, and SATB1 further mediates the long-distance interaction of the distal enhancer with the promoter. Deletion of the proximal enhancer decreases CCL5 expression and augments the cytotoxic activity of tissue-resident T and NK cells, which coincides with reduced melanoma metastasis in mouse models. By contrast, increased CCL5 expression resulting from RUNX3 mutation is associated with more tumor metastasis in the lung. Collectively, our results suggest that RUNX3-mediated CCL5 repression is critical for modulating anti-tumor immunity.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15375-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15375-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15375-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().