About: TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells
Creator	Fleskens, Veerle Durham, Lucy Evans, Hayley Roberts, Ceri Taams, Leonie Chatenoud, Lucienne
Source	Medline; PMC
abstract	CD4(+) and CD8(+) effector T cell subpopulations can display regulatory potential characterized by expression of the prototypically anti-inflammatory cytokine IL-10. However, the underlying cellular mechanisms that regulate expression of IL-10 in different T cell subpopulations are not yet fully elucidated. We recently showed that TNF inhibitors (TNFi) promote IL-10 expression in human CD4(+) T cells, including IL-17(+) CD4(+) T cells. Here, we further characterized the regulation of IL-10 expression via blockade of TNF signaling or other cytokine/co-stimulatory pathways, in human T cell subpopulations. Addition of the TNFi drug adalimumab to anti-CD3-stimulated human CD4(+) T cell/monocyte cocultures led to increased percentages of IL-10(+) cells in pro-inflammatory IL-17(+), IFNγ(+), TNFα(+), GM-CSF(+), and IL-4(+) CD4(+) T cell subpopulations. Conversely, exogenous TNFα strongly decreased IL-10(+) cell frequencies. TNF blockade also regulated IL-10 expression in CD4(+) T cells upon antigenic stimulation. Using time course experiments in whole peripheral blood mononuclear cell (PBMC) cultures, we show that TNF blockade maintained, rather than increased, IL-10(+) cell frequencies in both CD4(+) and CD8(+) T cells following in vitro stimulation in a dose- and time-dependent manner. Blockade of IL-17, IFNγ, IL-6R, or CD80/CD86-mediated co-stimulation did not significantly regulate IL-10 expression within CD4(+) or CD8(+) T cell subpopulations. We show that TNF blockade acts directly on effector CD4(+) T cells, in the absence of monocytes or CD4(+) CD25(high)CD127(low) regulatory T cells and independently of IL-27, resulting in higher IL-10(+) frequencies after 3 days in culture. IL-10/IL-10R blockade reduced the frequency of IL-10-expressing cells both in the presence and absence of TNF blockade. Addition of recombinant IL-10 alone was insufficient to drive an increase in IL-10(+) CD4(+) T cell frequencies in 3-day CD4(+) T cell/monocyte cocultures, but resulted in increased IL-10 expression at later time points in whole PBMC cultures. Together, these data provide additional insights into the regulation of IL-10 expression in human T cells by TNF blockade. The maintenance of an IL-10(+) phenotype across a broad range of effector T cell subsets may represent an underappreciated mechanism of action underlying this widely used therapeutic strategy.
has issue date	2017-02-15(xsd:dateTime)
bibo:doi	10.3389/fimmu.2017.00157
bibo:pmid	28261215
has license	cc-by
sha1sum (hex)	c0afcaab27d3532f3396316eb529468097bd6de7
schema:url	https://doi.org/10.3389/fimmu.2017.00157
resource representing a document's title	TNF Blockade Maintains an IL-10(+) Phenotype in Human Effector CD4(+) and CD8(+) T Cells
has PubMed Central identifier	PMC5309392
has PubMed identifier	28261215
schema:publication	Front Immunol
resource representing a document's body	covid:c0afcaab27d3532f3396316eb529468097bd6de7#body_text
is schema:about of	named entity 'cellular' named entity 'expressing' named entity 'acts' named entity 'frequencies' named entity 'adalimumab' named entity 'cell' named entity 'CD80' named entity 'IL-10' named entity 'monocyte' named entity 'IFNγ' named entity 'expression' named entity 'recombinant' named entity 'IL-17' named entity 'monocyte' named entity 'TNF' covid:arg/c0afcaab27d3532f3396316eb529468097bd6de7 named entity 'IL-17' named entity 'CD25' named entity 'USING' named entity 'IL-6R' named entity 'DOSE' named entity 'REGULATORY T CELLS' named entity 'CHARACTERIZED' named entity 'THESE' named entity 'ADALIMUMAB' named entity 'FULLY' named entity 'RATHER' named entity 'ADDITIONAL' named entity 'TNF' named entity 'DRIVE' named entity 'CD4' named entity 'RESULTING IN' named entity 'DRUG' named entity 'LATER' named entity 'INFLAMMATORY' named entity 'CD127' named entity 'POINTS' named entity 'PHENOTYPE' named entity 'HERE' named entity 'PATHWAYS' named entity 'FREQUENCIES' named entity '10%' named entity 'IFN' named entity 'CYTOKINE ' named entity 'TNF SIGNALING' named entity 'STRATEGY' named entity 'DAY' named entity 'ACROSS' named entity 'RECENTLY' named entity 'ARTICLE' named entity 'ORIGINAL' named entity 'MAINTAINED' named entity 'LED' named entity 'MEDIATED' named entity 'PERIPHERAL BLOOD MONONUCLEAR CELL' named entity 'CELLS' named entity 'PRESENCE' named entity 'DIRECTLY' named entity 'ANTI-CD3' named entity 'EFFECTOR' named entity 'IL-4' named entity 'STIMULATION' named entity 'IL-10' named entity 'CULTURES' named entity 'INCREASED' named entity 'MECHANISM OF ACTION' named entity 'IL-27' named entity 'EFFECTOR T CELL' named entity 'INSUFFICIENT' named entity 'TIME' named entity 'GM-CSF' named entity 'EXPRESSION' named entity 'CULTURE' named entity '10R' named entity 'PROMOTE' named entity 'EXOGENOUS'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2024 OpenLink Software