Epigenetic control of innate and adaptive immune memory [ATAC-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE108051 | GEO | 2018/05/29
REPOSITORIES: GEO
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Project description:Natural killer (NK) cells are innate lymphocytes that possess traits of adaptive immunity, such as clonal expansion, contraction, and generation of long-lived memory cells following viral infection. However, the molecular mechanisms by which clonally expanded effector NK (NKeff) cells persist to form memory cells is not well understood. Utilizing single cell RNA sequencing, we identify two Ly49H+ NKeff cell populations following mouse cytomegalovirus (MCMV) infection defined by the cell surface protein Ly6C. Ly6C– NKeff cells displayed enhanced survival during the contraction phase in a BCL2-dependent manner. Ly6C– NKeff cells displayed distinct transcriptional and epigenetic signatures compared to Ly6C+ NKeff cells, with a core epigenetic signature shared with memory precursor (MP) CD8+ T cells enriched in ETS1 and Fli1 DNA-binding motifs. Fli1 regulated memory NK cell fate by promoting terminal maturation and decreased persistence of contracting NK cells. Our results suggest that memory NK cells, similar to memory T cells, are generated by a subset of epigenetically distinct MP cell states that preferentially survive during the contraction phase of the response to viral infection.
2022-01-12 | GSE176208 | GEO
Project description:Natural Killer (NK) cells are innate cytotoxic lymphocytes with adaptive immune features, including antigen-specificity, clonal expansion, and memory. As such, NK cells share many transcriptional and epigenetic programs with their adaptive CD8+ T cell siblings. Various signals ranging from antigen, co-stimulation, and proinflammatory cytokines are required for optimal NK cell responses in mice and humans during virus infection; however, the integration of these signals remains unclear. In this study, we identified the transcription factor IRF4 as a signal integrator to coordinate the NK cell response during viral infection. Loss of IRF4 was detrimental to the expansion and differentiation of virus-specific NK cells. This defect was partially attributed to the inability of IRF4-deficient NK cells to uptake nutrients required for survival and memory generation. Altogether, these data suggest IRF4 is a signal integrator that acts as a secondary metabolic checkpoint to orchestrate the adaptive response of NK cells during viral infection.
2023-08-03 | GSE236555 | GEO
Project description:Natural Killer (NK) cells are innate cytotoxic lymphocytes with adaptive immune features, including antigen-specificity, clonal expansion, and memory. As such, NK cells share many transcriptional and epigenetic programs with their adaptive CD8+ T cell siblings. Various signals ranging from antigen, co-stimulation, and proinflammatory cytokines are required for optimal NK cell responses in mice and humans during virus infection; however, the integration of these signals remains unclear. In this study, we identified the transcription factor IRF4 as a signal integrator to coordinate the NK cell response during viral infection. Loss of IRF4 was detrimental to the expansion and differentiation of virus-specific NK cells. This defect was partially attributed to the inability of IRF4-deficient NK cells to uptake nutrients required for survival and memory generation. Altogether, these data suggest IRF4 is a signal integrator that acts as a secondary metabolic checkpoint to orchestrate the adaptive response of NK cells during viral infection.
2023-08-03 | GSE235064 | GEO
Project description:Natural killer (NK) cells are innate lymphocytes that possess features of adaptive immunity such as clonal expansion and generation of long-lived memory. Here we look at transcriptional profiles of NK cells throughout several time points during MCMV infection, ex-vivo cytokine stimulation, and/or deficiency of key transcription factors such as STAT4, STAT1, and Runx1. In addition, we profile parallel time points of MCMV-specific CD8 T cells during infection and memory formation.
2017-12-20 | GSE106138 | GEO
Project description:Natural killer (NK) cells are innate lymphocytes with the capacity to elicit adaptive features, including clonal expansion and immunological memory. Because signal transducer and activator of transcription 5 (STAT5) is essential for NK cell development, the role of this transcription factor and its upstream cytokines IL-2 and IL-15 during infection have not been carefully investigated. In this study, we investigate how STAT5 regulates transcription during viral infection. We demonstrate that STAT5 is induced in NK cells by IL-12 and STAT4 early after infection, and that partial STAT5 deficiency results in a defective capacity of NK cells to generate long-lived memory cells. Furthermore, we find a functional dichotomy of IL-2 and IL-15 signaling outputs during viral infection, whereby both cytokines drive clonal expansion, but only IL-15 is required for memory NK cell survival. We thus highlight a novel role for STAT5 signaling in promoting an optimal antiviral NK cell response.
2020-12-27 | GSE142821 | GEO
Project description:Here we show that Zika virus infection induces memory like NK cells that express CD27. This subset shared transcriptional changes with memory CD8 T cells, stem cells and stem like T cells. These NK cells with memory and stemness features which we term NK memory stem cells (SCMNK) demonstrated greater antiviral potential. Transcriptional data of SCMNK and non-memory NK cells is presented.
2020-12-11 | GSE148205 | GEO
Project description:This a model from the article:
Dynamics of killer T cell inflation in viral infections.
Wodarz D, Sierro S, Klenerman P. J R Soc Interface
2007 Jun 22;4(14):533-43 17251133
,
Abstract:
Upon acute viral infection, a typical cytotoxic T lymphocyte (CTL) response is
characterized by a phase of expansion and contraction after which it settles at
a relatively stable memory level. Recently, experimental data from mice infected
with murine cytomegalovirus (MCMV) showed different and unusual dynamics. After
acute infection had resolved, some antigen specific CTL started to expand over
time despite the fact that no replicative virus was detectable. This phenomenon
has been termed as "CTL memory inflation". In order to examine the dynamics of
this system further, we developed a mathematical model analysing the impact of
innate and adaptive immune responses. According to this model, a potentially
important contributor to CTL inflation is competition between the specific CTL
response and an innate natural killer (NK) cell response. Inflation occurs most
readily if the NK cell response is more efficient than the CTL at reducing virus
load during acute infection, but thereafter maintains a chronic virus load which
is sufficient to induce CTL proliferation. The model further suggests that
weaker NK cell mediated protection can correlate with more pronounced CTL
inflation dynamics over time. We present experimental data from mice infected
with MCMV which are consistent with the theoretical predictions. This model
provides valuable information and may help to explain the inflation of CMV
specific CD8+T cells seen in humans as they age.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Wodarz D, Sierro S, Klenerman P. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2010-06-25 | BIOMD0000000686 | BioModels
Project description:This a model from the article:
Dynamics of killer T cell inflation in viral infections.
Wodarz D, Sierro S, Klenerman P. J R Soc Interface
2007 Jun 22;4(14):533-43 17251133
,
Abstract:
Upon acute viral infection, a typical cytotoxic T lymphocyte (CTL) response is
characterized by a phase of expansion and contraction after which it settles at
a relatively stable memory level. Recently, experimental data from mice infected
with murine cytomegalovirus (MCMV) showed different and unusual dynamics. After
acute infection had resolved, some antigen specific CTL started to expand over
time despite the fact that no replicative virus was detectable. This phenomenon
has been termed as "CTL memory inflation". In order to examine the dynamics of
this system further, we developed a mathematical model analysing the impact of
innate and adaptive immune responses. According to this model, a potentially
important contributor to CTL inflation is competition between the specific CTL
response and an innate natural killer (NK) cell response. Inflation occurs most
readily if the NK cell response is more efficient than the CTL at reducing virus
load during acute infection, but thereafter maintains a chronic virus load which
is sufficient to induce CTL proliferation. The model further suggests that
weaker NK cell mediated protection can correlate with more pronounced CTL
inflation dynamics over time. We present experimental data from mice infected
with MCMV which are consistent with the theoretical predictions. This model
provides valuable information and may help to explain the inflation of CMV
specific CD8+T cells seen in humans as they age.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Wodarz D, Sierro S, Klenerman P. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2010-06-25 | BIOMD0000000687 | BioModels
Project description:This a model from the article:
Dynamics of killer T cell inflation in viral infections.
Wodarz D, Sierro S, Klenerman P. J R Soc Interface
2007 Jun 22;4(14):533-43 17251133
,
Abstract:
Upon acute viral infection, a typical cytotoxic T lymphocyte (CTL) response is
characterized by a phase of expansion and contraction after which it settles at
a relatively stable memory level. Recently, experimental data from mice infected
with murine cytomegalovirus (MCMV) showed different and unusual dynamics. After
acute infection had resolved, some antigen specific CTL started to expand over
time despite the fact that no replicative virus was detectable. This phenomenon
has been termed as "CTL memory inflation". In order to examine the dynamics of
this system further, we developed a mathematical model analysing the impact of
innate and adaptive immune responses. According to this model, a potentially
important contributor to CTL inflation is competition between the specific CTL
response and an innate natural killer (NK) cell response. Inflation occurs most
readily if the NK cell response is more efficient than the CTL at reducing virus
load during acute infection, but thereafter maintains a chronic virus load which
is sufficient to induce CTL proliferation. The model further suggests that
weaker NK cell mediated protection can correlate with more pronounced CTL
inflation dynamics over time. We present experimental data from mice infected
with MCMV which are consistent with the theoretical predictions. This model
provides valuable information and may help to explain the inflation of CMV
specific CD8+T cells seen in humans as they age.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Wodarz D, Sierro S, Klenerman P. (2007) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2010-06-25 | BIOMD0000000688 | BioModels
Project description:Miao2010 - Innate and adaptive immune
responses to primary Influenza A Virus infection
This model is described in the article:
Quantifying the early immune
response and adaptive immune response kinetics in mice infected
with influenza A virus.
Miao H, Hollenbaugh JA, Zand MS,
Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ.
J. Virol. 2010 Jul; 84(13):
6687-6698
Abstract:
Seasonal and pandemic influenza A virus (IAV) continues to
be a public health threat. However, we lack a detailed and
quantitative understanding of the immune response kinetics to
IAV infection and which biological parameters most strongly
influence infection outcomes. To address these issues, we use
modeling approaches combined with experimental data to
quantitatively investigate the innate and adaptive immune
responses to primary IAV infection. Mathematical models were
developed to describe the dynamic interactions between target
(epithelial) cells, influenza virus, cytotoxic T lymphocytes
(CTLs), and virus-specific IgG and IgM. IAV and immune kinetic
parameters were estimated by fitting models to a large data set
obtained from primary H3N2 IAV infection of 340 mice. Prior to
a detectable virus-specific immune response (before day 5), the
estimated half-life of infected epithelial cells is
approximately 1.2 days, and the half-life of free infectious
IAV is approximately 4 h. During the adaptive immune response
(after day 5), the average half-life of infected epithelial
cells is approximately 0.5 days, and the average half-life of
free infectious virus is approximately 1.8 min. During the
adaptive phase, model fitting confirms that CD8(+) CTLs are
crucial for limiting infected cells, while virus-specific IgM
regulates free IAV levels. This may imply that CD4 T cells and
class-switched IgG antibodies are more relevant for generating
IAV-specific memory and preventing future infection via a more
rapid secondary immune response. Also, simulation studies were
performed to understand the relative contributions of
biological parameters to IAV clearance. This study provides a
basis to better understand and predict influenza virus
immunity.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000546.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2021-10-05 | BIOMD0000000546 | BioModels