Repository logo
 

NFIL3 contributes to cytotoxic T lymphocyte-mediated killing.

Published version
Peer-reviewed

Repository DOI


Change log

Authors

Strege, Katharina 
Del Castillo Velasco-Herrera, Martin 
Adams, David J 

Abstract

Cytotoxic T lymphocytes (CTLs) are key effectors of the adaptive immune system that recognize and eliminate virally infected and cancerous cells. In naive CD8+ T cells, T-cell receptor (TCR) engagement drives a number of transcriptional, translational and proliferation changes over the course of hours and days leading to differentiation into CTLs. To gain a better insight into this mechanism, we compared the transcriptional profiles of naive CD8+ T cells to those of activated CTLs. To find new regulators of CTL function, we performed a selective clustered regularly interspaced short palindromic repeats (CRISPR) screen on upregulated genes and identified nuclear factor IL-3 (NFIL3) as a potential regulator of cytotoxicity. Although NFIL3 has established roles in several immune cells including natural killer, Treg, dendritic and CD4+ T cells, its function in CD8+ CTLs is less well understood. Using CRISPR/Cas9 editing, we found that removing NFIL3 in CTLs resulted in a marked decrease in cytotoxicity. We found that in CTLs lacking NFIL3 TCR-induced extracellular signal-regulated kinase phosphorylation, immune synapse formation and granule release were all intact while cytotoxicity was functionally impaired in vitro. Strikingly, NFIL3 controls the production of cytolytic proteins as well as effector cytokines. Thus, NFIL3 plays a cell intrinsic role in modulating cytolytic mechanisms in CTLs.

Description

Peer reviewed: True


Publication status: Published


Funder: Bettencourt Schueller Foundation

Keywords

NFIL3, T-cell-mediated killing, autoimmunity, cytotoxic T cell, granzyme, perforin, T-Lymphocytes, Cytotoxic, CD8-Positive T-Lymphocytes, Interleukin-3, Perforin, Receptors, Antigen, T-Cell

Journal Title

Open Biol

Conference Name

Journal ISSN

2046-2441
2046-2441

Volume Title

14

Publisher

The Royal Society
Sponsorship
Wellcome Trust (217100/Z/19/Z)
Wellcome Trust (100140/Z/12/Z)