Cargando…

Identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli

INTRODUCTION: Neutrophils represent the largest proportion of circulating leukocytes and, in response to inflammatory stimuli, are rapidly recruited to sites of infection where they neutralize pathogens. METHODS AND RESULTS: We have identified a novel neutrophil transcription network induced in resp...

Descripción completa

Detalles Bibliográficos
Autores principales: Ismailova, Aiten, Salehi-Tabar, Reyhaneh, Dimitrov, Vassil, Memari, Babak, Barbier, Camille, White, John H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900176/
https://www.ncbi.nlm.nih.gov/pubmed/36756115
http://dx.doi.org/10.3389/fimmu.2023.1123344
_version_ 1784882791426555904
author Ismailova, Aiten
Salehi-Tabar, Reyhaneh
Dimitrov, Vassil
Memari, Babak
Barbier, Camille
White, John H.
author_facet Ismailova, Aiten
Salehi-Tabar, Reyhaneh
Dimitrov, Vassil
Memari, Babak
Barbier, Camille
White, John H.
author_sort Ismailova, Aiten
collection PubMed
description INTRODUCTION: Neutrophils represent the largest proportion of circulating leukocytes and, in response to inflammatory stimuli, are rapidly recruited to sites of infection where they neutralize pathogens. METHODS AND RESULTS: We have identified a novel neutrophil transcription network induced in response to inflammatory stimuli. We performed the first RNAseq analysis of human neutrophils exposed to lipopolysaccharide (LPS), followed by a meta-analysis of our dataset and previously published studies of LPS-challenged neutrophils. This revealed a robustly enhanced transcriptional network driven by forkhead box (FOX) transcription factors. The network is enriched in genes encoding proinflammatory cytokines and transcription factors, including MAFF and ATF3, which are implicated in responses to stress, survival and inflammation. Expression of transcription factors FOXP1 and FOXP4 is induced in neutrophils exposed to inflammatory stimuli, and potential FOXP1/FOXP4 binding sites were identified in several genes in the network, all located in chromatin regions consistent with neutrophil enhancer function. Chromatin immunoprecipitation (ChIP) assays in neutrophils confirmed enhanced binding of FOXP4, but not FOXP1, to multiple sites in response to LPS. Binding to numerous motifs and transactivation of network genes were also observed when FOXP proteins were transiently expressed in HEK293 cells. In addition to LPS, the transcriptional network is induced by other inflammatory stimuli, indicating it represents a general neutrophil response to inflammation. DISCUSSION: Collectively, these findings reveal a role for the FOXP4 transcription network as a regulator of responses to inflammatory stimuli in neutrophils.
format Online
Article
Text
id pubmed-9900176
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-99001762023-02-07 Identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli Ismailova, Aiten Salehi-Tabar, Reyhaneh Dimitrov, Vassil Memari, Babak Barbier, Camille White, John H. Front Immunol Immunology INTRODUCTION: Neutrophils represent the largest proportion of circulating leukocytes and, in response to inflammatory stimuli, are rapidly recruited to sites of infection where they neutralize pathogens. METHODS AND RESULTS: We have identified a novel neutrophil transcription network induced in response to inflammatory stimuli. We performed the first RNAseq analysis of human neutrophils exposed to lipopolysaccharide (LPS), followed by a meta-analysis of our dataset and previously published studies of LPS-challenged neutrophils. This revealed a robustly enhanced transcriptional network driven by forkhead box (FOX) transcription factors. The network is enriched in genes encoding proinflammatory cytokines and transcription factors, including MAFF and ATF3, which are implicated in responses to stress, survival and inflammation. Expression of transcription factors FOXP1 and FOXP4 is induced in neutrophils exposed to inflammatory stimuli, and potential FOXP1/FOXP4 binding sites were identified in several genes in the network, all located in chromatin regions consistent with neutrophil enhancer function. Chromatin immunoprecipitation (ChIP) assays in neutrophils confirmed enhanced binding of FOXP4, but not FOXP1, to multiple sites in response to LPS. Binding to numerous motifs and transactivation of network genes were also observed when FOXP proteins were transiently expressed in HEK293 cells. In addition to LPS, the transcriptional network is induced by other inflammatory stimuli, indicating it represents a general neutrophil response to inflammation. DISCUSSION: Collectively, these findings reveal a role for the FOXP4 transcription network as a regulator of responses to inflammatory stimuli in neutrophils. Frontiers Media S.A. 2023-01-20 /pmc/articles/PMC9900176/ /pubmed/36756115 http://dx.doi.org/10.3389/fimmu.2023.1123344 Text en Copyright © 2023 Ismailova, Salehi-Tabar, Dimitrov, Memari, Barbier and White https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ismailova, Aiten
Salehi-Tabar, Reyhaneh
Dimitrov, Vassil
Memari, Babak
Barbier, Camille
White, John H.
Identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli
title Identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli
title_full Identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli
title_fullStr Identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli
title_full_unstemmed Identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli
title_short Identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli
title_sort identification of a forkhead box protein transcriptional network induced in human neutrophils in response to inflammatory stimuli
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900176/
https://www.ncbi.nlm.nih.gov/pubmed/36756115
http://dx.doi.org/10.3389/fimmu.2023.1123344
work_keys_str_mv AT ismailovaaiten identificationofaforkheadboxproteintranscriptionalnetworkinducedinhumanneutrophilsinresponsetoinflammatorystimuli
AT salehitabarreyhaneh identificationofaforkheadboxproteintranscriptionalnetworkinducedinhumanneutrophilsinresponsetoinflammatorystimuli
AT dimitrovvassil identificationofaforkheadboxproteintranscriptionalnetworkinducedinhumanneutrophilsinresponsetoinflammatorystimuli
AT memaribabak identificationofaforkheadboxproteintranscriptionalnetworkinducedinhumanneutrophilsinresponsetoinflammatorystimuli
AT barbiercamille identificationofaforkheadboxproteintranscriptionalnetworkinducedinhumanneutrophilsinresponsetoinflammatorystimuli
AT whitejohnh identificationofaforkheadboxproteintranscriptionalnetworkinducedinhumanneutrophilsinresponsetoinflammatorystimuli