Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals.

PubWeight™: 1.83‹?› | Rank: Top 3%

🔗 View Article (PMC 2118423)

Published in J Exp Med on January 16, 2007

Authors

Alejandro V Villarino1, Cristina M Tato, Jason S Stumhofer, Zhengju Yao, Yongzhi K Cui, Lothar Hennighausen, John J O'Shea, Christopher A Hunter

Author Affiliations

1: Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA 19104, USA. alejandro.villarino@ucsf.edu

Articles citing this

The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol (2009) 6.74

Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity (2008) 6.08

Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity (2009) 4.85

IL-12 family cytokines: immunological playmakers. Nat Immunol (2012) 3.12

Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol (2011) 2.59

Aiolos promotes TH17 differentiation by directly silencing Il2 expression. Nat Immunol (2012) 2.49

Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response. Mol Syst Biol (2010) 2.21

Blimp-1 directly represses Il2 and the Il2 activator Fos, attenuating T cell proliferation and survival. J Exp Med (2008) 2.00

An intense form of homeostatic proliferation of naive CD8+ cells driven by IL-2. J Exp Med (2007) 1.59

Soluble IL-2RA levels in multiple sclerosis subjects and the effect of soluble IL-2RA on immune responses. J Immunol (2009) 1.55

Induction of PP2A Bβ, a regulator of IL-2 deprivation-induced T-cell apoptosis, is deficient in systemic lupus erythematosus. Proc Natl Acad Sci U S A (2011) 1.49

Molecular mechanisms of treg-mediated T cell suppression. Front Immunol (2012) 1.41

CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T cell homeostasis in mice. J Clin Invest (2011) 1.39

CD4 memory T cells divide poorly in response to antigen because of their cytokine profile. Proc Natl Acad Sci U S A (2008) 1.25

STAT3 protein promotes T-cell survival and inhibits interleukin-2 production through up-regulation of Class O Forkhead transcription factors. J Biol Chem (2011) 1.22

The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells. Immunity (2015) 1.20

The IL-2/CD25 pathway determines susceptibility to T1D in humans and NOD mice. J Clin Immunol (2008) 1.19

Diversity and plasticity of Th cell types predicted from regulatory network modelling. PLoS Comput Biol (2010) 1.17

Baseline levels of influenza-specific CD4 memory T-cells affect T-cell responses to influenza vaccines. PLoS One (2008) 1.11

Loss of Jak2 selectively suppresses DC-mediated innate immune response and protects mice from lethal dose of LPS-induced septic shock. PLoS One (2010) 1.07

Biphasic regulation of Il2 transcription in CD4+ T cells: roles for TNF-alpha receptor signaling and chromatin structure. J Immunol (2008) 1.07

Erythropoietin receptor response circuits. Curr Opin Hematol (2010) 1.07

Novel IL27p28/IL12p40 cytokine suppressed experimental autoimmune uveitis by inhibiting autoreactive Th1/Th17 cells and promoting expansion of regulatory T cells. J Biol Chem (2012) 1.04

An artificial antigen-presenting cell with paracrine delivery of IL-2 impacts the magnitude and direction of the T cell response. J Biol Chem (2011) 1.03

T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks. Elife (2014) 1.02

Constitutively active Stat5b in CD4+ T cells inhibits graft-versus-host disease lethality associated with increased regulatory T-cell potency and decreased T effector cell responses. Blood (2010) 1.01

Genomic dissection of the cytokine-controlled STAT5 signaling network in liver. Physiol Genomics (2008) 0.99

Production of interleukin-27 by human neutrophils regulates their function during bacterial infection. Eur J Immunol (2012) 0.97

IL-2 coordinates IL-2-producing and regulatory T cell interplay. J Exp Med (2013) 0.97

Soluble IL-2Rα (sCD25) exacerbates autoimmunity and enhances the development of Th17 responses in mice. PLoS One (2012) 0.94

A pivotal role for interleukin-27 in CD8+ T cell functions and generation of cytotoxic T lymphocytes. J Biomed Biotechnol (2010) 0.93

Activated human T cells secrete exosomes that participate in IL-2 mediated immune response signaling. PLoS One (2012) 0.93

Microbe-dendritic cell dialog controls regulatory T-cell fate. Immunol Rev (2010) 0.92

Negative feedback regulation of T cells via interleukin-2 and FOXP3 reciprocity. PLoS One (2008) 0.88

A novel function of IL-2: chemokine/chemoattractant/retention receptor genes induction in Th subsets for skin and lung inflammation. J Autoimmun (2012) 0.86

Vaccine-induced antibody isotypes are skewed by impaired CD4 T cell and invariant NKT cell effector responses in MyD88-deficient mice. J Immunol (2009) 0.85

Signal transducer and activator of transcription 5 (STAT5) paralog dose governs T cell effector and regulatory functions. Elife (2016) 0.81

Association of IL-27 gene three polymorphisms with Crohn's disease susceptibility in a Chinese Han population. Int J Clin Exp Pathol (2014) 0.81

Astragaloside II triggers T cell activation through regulation of CD45 protein tyrosine phosphatase activity. Acta Pharmacol Sin (2013) 0.80

Stable IL-2 decision making by endogenous c-Fos amounts in peripheral memory T-helper cells. J Biol Chem (2012) 0.80

Annexin A6 regulates interleukin-2-mediated T-cell proliferation. Immunol Cell Biol (2016) 0.78

Differential cytokine sensitivities of STAT5-dependent enhancers rely on Stat5 autoregulation. Nucleic Acids Res (2016) 0.77

Using an adaptive gene network model for self-organizing multicellular behavior. Conf Proc IEEE Eng Med Biol Soc (2012) 0.77

Inhibition of G-protein βγ signaling enhances T cell receptor-stimulated interleukin 2 transcription in CD4+ T helper cells. PLoS One (2015) 0.77

In vivo suppression of naive CD4 T cell responses by IL-2- and antigen-stimulated T lymphocytes in the absence of APC competition. J Immunol (2008) 0.77

Inhibition of G-Protein βγ Signaling Decreases Levels of Messenger RNAs Encoding Proinflammatory Cytokines in T Cell Receptor-Stimulated CD4(+) T Helper Cells. J Mol Signal (2015) 0.75

Adequate immune response ensured by binary IL-2 and graded CD25 expression in a murine transfer model. Elife (2016) 0.75

Mechanisms and consequences of Jak-STAT signaling in the immune system. Nat Immunol (2017) 0.75

Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis. Biologics (2016) 0.75

mTORC1 regulates mannose-6-phosphate receptor transport and T-cell vulnerability to regulatory T cells by controlling kinesin KIF13A. Cell Discov (2017) 0.75

Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma. Heliyon (2017) 0.75

Articles cited by this

The B7 family revisited. Annu Rev Immunol (2005) 13.51

Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med (1985) 8.21

Interleukin-2: inception, impact, and implications. Science (1988) 8.19

Regulation of lymphokine messenger RNA stability by a surface-mediated T cell activation pathway. Science (1989) 7.78

Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature (2006) 5.90

Interleukin-2 programs mouse alpha beta T lymphocytes for apoptosis. Nature (1991) 5.80

Tolerance, not immunity, crucially depends on IL-2. Nat Rev Immunol (2004) 5.24

Purification and some characteristics of human T-cell growth factor from phytohemagglutinin-stimulated lymphocyte-conditioned media. Proc Natl Acad Sci U S A (1980) 4.91

Selective, stable demethylation of the interleukin-2 gene enhances transcription by an active process. Nat Immunol (2003) 4.83

New IL-12-family members: IL-23 and IL-27, cytokines with divergent functions. Nat Rev Immunol (2005) 4.53

Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen. J Exp Med (2005) 3.70

Stat5a/b are essential for normal lymphoid development and differentiation. Proc Natl Acad Sci U S A (2006) 3.66

Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity (2001) 3.45

Transcriptional regulation of the IL-2 gene. Curr Opin Immunol (1995) 3.14

Tob is a negative regulator of activation that is expressed in anergic and quiescent T cells. Nat Immunol (2001) 2.97

Cytokines and immunodeficiency diseases. Nat Rev Immunol (2001) 2.86

Stat5 activation plays a critical role in Th2 differentiation. Immunity (2003) 2.80

NF-kappa B subunit regulation in nontransformed CD4+ T lymphocytes. Science (1992) 2.69

Control of biologically active interleukin 2 messenger RNA formation in induced human lymphocytes. Proc Natl Acad Sci U S A (1984) 2.17

IL-27 limits IL-2 production during Th1 differentiation. J Immunol (2006) 1.89

IL-2 secretion by CD4+ T cells in vivo is rapid, transient, and influenced by TCR-specific competition. J Immunol (2004) 1.74

p27kip1 functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes. Nat Med (2000) 1.73

Interleukin 4 suppresses interleukin 2 and interferon gamma production by naive T cells stimulated by accessory cell-dependent receptor engagement. Proc Natl Acad Sci U S A (1993) 1.71

IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508. J Exp Med (2005) 1.64

IL-7: maintaining T-cell memory and achieving homeostasis. Trends Immunol (2005) 1.55

In vivo priming of CD4 T cells that produce interleukin (IL)-2 but not IL-4 or interferon (IFN)-gamma, and can subsequently differentiate into IL-4- or IFN-gamma-secreting cells. J Exp Med (2001) 1.42

T(H)1 and T(H)2 cells: a historical perspective. Nat Rev Immunol (2002) 1.40

Smad3 is essential for TGF-beta 1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferation. J Immunol (2004) 1.24

Interleukin-2 induced immune effects in human immunodeficiency virus-infected patients receiving intermittent interleukin-2 immunotherapy. Eur J Immunol (2001) 1.20

The interleukin-4 receptor activates STAT5 by a mechanism that relies upon common gamma-chain. J Biol Chem (1998) 1.00

Articles by these authors

Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity (2007) 12.12

TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat Immunol (2007) 11.14

Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. Immunity (2009) 9.73

Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol (2006) 7.89

Control of effector CD8+ T cell function by the transcription factor Eomesodermin. Science (2003) 7.75

Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling. Nature (2010) 7.50

Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol (2010) 6.88

The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol (2009) 6.74

Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol (2007) 5.99

Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells. Proc Natl Acad Sci U S A (2006) 5.69

The IL-27R (WSX-1) is required to suppress T cell hyperactivity during infection. Immunity (2003) 5.60

De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum (2002) 4.98

Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med (2008) 4.95

Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol (2007) 4.90

Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest (2006) 4.77

IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem (2007) 4.77

Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood (2007) 4.50

Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation. Mol Cell Biol (2004) 4.45

Anomalous type 17 response to viral infection by CD8+ T cells lacking T-bet and eomesodermin. Science (2008) 4.04

Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol (2011) 3.91

Stat5a/b are essential for normal lymphoid development and differentiation. Proc Natl Acad Sci U S A (2006) 3.66

Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nat Immunol (2002) 3.60

Janus kinases in immune cell signaling. Immunol Rev (2009) 3.60

Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity (2010) 3.52

Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J Exp Med (2006) 3.36

Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood (2007) 3.33

Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity (2011) 3.24

Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science (2003) 3.19

Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Immunol Rev (2004) 3.18

An adjunct mammary epithelial cell population in parous females: its role in functional adaptation and tissue renewal. Development (2002) 3.16

IFN regulatory factor-4 and -8 govern dendritic cell subset development and their functional diversity. J Immunol (2005) 3.15

Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum (2007) 3.06

Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection. Science (2002) 3.05

Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights. J Clin Immunol (2003) 2.93

Inflammasome-mediated disease animal models reveal roles for innate but not adaptive immunity. Immunity (2009) 2.93

Genetic evidence supporting selection of the Valpha14i NKT cell lineage from double-positive thymocyte precursors. Immunity (2005) 2.72

CD4+ FoxP3+ regulatory T cells confer infectious tolerance in a TGF-beta-dependent manner. J Exp Med (2008) 2.72

Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation. Immunity (2010) 2.70

T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J Exp Med (2006) 2.70

Activation of PPAR gamma and delta by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterology (2004) 2.65

The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev (2003) 2.62

Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol (2011) 2.59

The cytokines interleukin 27 and interferon-γ promote distinct Treg cell populations required to limit infection-induced pathology. Immunity (2012) 2.52

Interleukin-27 priming of T cells controls IL-17 production in trans via induction of the ligand PD-L1. Immunity (2012) 2.47

Th17 cells: a new fate for differentiating helper T cells. Immunol Res (2008) 2.45

STATs shape the active enhancer landscape of T cell populations. Cell (2012) 2.45

Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development (2002) 2.42

T(H)-17 differentiation: of mice and men. Nat Immunol (2007) 2.40

IL-27 blocks RORc expression to inhibit lineage commitment of Th17 cells. J Immunol (2009) 2.39

Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells. Nature (2012) 2.38

Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation. Blood (2006) 2.38

TGF-β and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nat Immunol (2012) 2.37

IL-23 provides a limited mechanism of resistance to acute toxoplasmosis in the absence of IL-12. J Immunol (2004) 2.37

BACH2 represses effector programs to stabilize T(reg)-mediated immune homeostasis. Nature (2013) 2.36

TRAF6 is a critical factor for dendritic cell maturation and development. Immunity (2003) 2.36

RIP-Cre revisited, evidence for impairments of pancreatic beta-cell function. J Biol Chem (2005) 2.32

Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells. FASEB J (2002) 2.26

Stat5 is indispensable for the maintenance of bcr/abl-positive leukaemia. EMBO Mol Med (2010) 2.23

Helminth antigens modulate TLR-initiated dendritic cell activation. J Immunol (2004) 2.21

Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells. Nat Immunol (2010) 2.19

Hepatocyte-specific disruption of Bcl-xL leads to continuous hepatocyte apoptosis and liver fibrotic responses. Gastroenterology (2004) 2.18

The Janus kinases (Jaks). Genome Biol (2004) 2.18

Trafficking of immune cells in the central nervous system. J Clin Invest (2010) 2.17

Postnatal body growth is dependent on the transcription factors signal transducers and activators of transcription 5a/b in muscle: a role for autocrine/paracrine insulin-like growth factor I. Endocrinology (2006) 2.10

The IL-27 receptor (WSX-1) is an inhibitor of innate and adaptive elements of type 2 immunity. J Immunol (2004) 2.09

Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticity. Annu Rev Immunol (2012) 2.06

A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8⁺ T-cell accumulation in the skin. J Invest Dermatol (2012) 2.05

Therapeutic targeting of Janus kinases. Immunol Rev (2008) 2.03

Hematopoietic-specific Stat5-null mice display microcytic hypochromic anemia associated with reduced transferrin receptor gene expression. Blood (2008) 2.01

Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cells. Nat Immunol (2009) 1.98

NF-kappaB family of transcription factors: central regulators of innate and adaptive immune functions. Clin Microbiol Rev (2002) 1.97

Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis. Cancer Res (2002) 1.96

Selectivity and therapeutic inhibition of kinases: to be or not to be? Nat Immunol (2009) 1.92

IL-27 limits IL-2 production during Th1 differentiation. J Immunol (2006) 1.89

Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation. Semin Immunol (2007) 1.87

A critical role for IL-10 in limiting inflammation during toxoplasmic encephalitis. J Neuroimmunol (2005) 1.86

Behavior of parasite-specific effector CD8+ T cells in the brain and visualization of a kinesis-associated system of reticular fibers. Immunity (2009) 1.84

Cutting edge: dendritic cell-restricted antigen presentation initiates the follicular helper T cell program but cannot complete ultimate effector differentiation. J Immunol (2011) 1.84

Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells. Immunity (2011) 1.83

The canonical Notch/RBP-J signaling pathway controls the balance of cell lineages in mammary epithelium during pregnancy. Dev Biol (2006) 1.80