The biology of IL-12: coordinating innate and adaptive immune responses

Toll-like receptors: critical proteins linking innate and acquired immunity

2001 • 4,673 citations

Toll-like receptors and innate immunity

2001 • 4,138 citations

Novel p19 Protein Engages IL-12p40 to Form a Cytokine, IL-23, with Biological Activities Similar as Well as Distinct from IL-12

2000 • 2,755 citations

Ligation of CD40 on dendritic cells triggers production of high levels of interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC activation.

1996 • 2,032 citations

JAKS AND STATS: Biological Implications

1998 • 1,788 citations

IL-27, a Heterodimeric Cytokine Composed of EBI3 and p28 Protein, Induces Proliferation of Naive CD4+ T Cells

2002 • 1,401 citations

Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice

1996 • 1,277 citations

A Receptor for the Heterodimeric Cytokine IL-23 Is Composed of IL-12Rβ1 and a Novel Cytokine Receptor Subunit, IL-23R

2002 • 1,238 citations

Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells

1996 • 1,182 citations

Jak2 Is Essential for Signaling through a Variety of Cytokine Receptors

1998 • 1,155 citations

Cytokine Signaling in 2002

2002 • 1,089 citations

Regulation of the Interleukin (IL)-12R β2 Subunit Expression in Developing T Helper 1 (Th1) and Th2 Cells

1997 • 1,022 citations

IL-12-Deficient Mice Are Defective in IFNγ Production and Type 1 Cytokine Responses

1996 • 991 citations

T-bet is a STAT1-induced regulator of IL-12R expression in naïve CD4+ T cells

2002 • 985 citations

High level IL-12 production by murine dendritic cells: upregulation via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10.

1996 • 959 citations

Jak2 Deficiency Defines an EssentialDevelopmental Checkpoint in DefinitiveHematopoiesis

1998 • 904 citations

Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells.

1991 • 861 citations

Severe Mycobacterial and Salmonella Infections in Interleukin-12 Receptor-Deficient Patients

1998 • 812 citations

Selective Expression of an Interleukin-12 Receptor Component by Human T Helper 1 Cells

1997 • 783 citations

T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells

2001 • 743 citations

IGIF Does Not Drive Th1 Development but Synergizes with IL-12 for Interferon-γ Production and Activates IRAK and NFκB

1997 • 726 citations

A functional interleukin 12 receptor complex is composed of two β-type cytokine receptor subunits

1996 • 690 citations

Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4.

1995 • 675 citations

The interleukin 12 p40 gene promoter is primed by interferon gamma in monocytic cells.

1996 • 663 citations

Interferon‐γ‐inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin‐12 for interferon‐γ production

1996 • 606 citations

Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor.

1991 • 593 citations

Regulation of Interleukin 12 p40 Expression through an NF-κB Half-Site

1995 • 495 citations

Cooperative DNA Binding and Sequence-Selective Recognition Conferred by the STAT Amino-Terminal Domain

1996 • 483 citations

Genetically resistant mice lacking interleukin‐12 are susceptible to infection with Leishmania major and mount a polarized Th2 cell response

1996 • 483 citations

Critical Role for STAT4 Activation by Type 1 Interferons in the Interferon-γ Response to Viral Infection

2002 • 476 citations

Cutting Edge: MyD88 Is Required for Resistance toToxoplasma gondiiInfection and Regulates Parasite-Induced IL-12 Production by Dendritic Cells

2002 • 476 citations

Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor).

1991 • 471 citations

IFN-γ production by antigen-presenting cells: mechanisms emerge

2001 • 456 citations

Interleukin 12 induces tyrosine phosphorylation and activation of STAT4 in human lymphocytes.

1995 • 446 citations

Partial Impairment of Cytokine Responses in Tyk2-Deficient Mice

2000 • 412 citations

WSX-1 Is Required for the Initiation of Th1 Responses and Resistance to L. major Infection

2001 • 409 citations

Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity.

1995 • 407 citations

Development of Th1-type immune responses requires the type I cytokine receptor TCCR

2000 • 394 citations

Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-γ production from activated B cells

1997 • 385 citations

Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12

2002 • 382 citations

Interleukin (Il)-4 Is a Major Regulatory Cytokine Governing Bioactive IL-12 Production by Mouse and Human Dendritic Cells

2000 • 376 citations

Stimulatory and inhibitory effects of interleukin (IL)-4 and IL-13 on the production of cytokines by human peripheral blood mononuclear cells: priming for IL-12 and tumor necrosis factor alpha production.

1995 • 372 citations

Interleukin 12 (IL-12) induces tyrosine phosphorylation of JAK2 and TYK2: differential use of Janus family tyrosine kinases by IL-2 and IL-12.

1995 • 350 citations

Control of adaptive immune responses by Toll-like receptors

2002 • 335 citations

Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12

2002 • 332 citations

A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes

1996 • 327 citations

Tyk2 Plays a Restricted Role in IFNα Signaling, Although It Is Required for IL-12-Mediated T Cell Function

2000 • 310 citations

Multiple Control Elements Mediate Activation of the Murine and Human Interleukin 12 p40 Promoters: Evidence of Functional Synergy between C/EBP and Rel Proteins

1997 • 310 citations

Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130.

1994 • 309 citations

Epstein–Barr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin

1997 • 308 citations

Regulation of bioactive IL-12 production in lipopolysaccharide-stimulated human monocytes is determined by the expression of the p35 subunit.

1996 • 306 citations

Interleukin-12 Is Essential for a Protective Th1 Response in Mice Infected withCryptococcus neoformans

1998 • 303 citations

Selective requirement for c-Rel during IL-12 P40 gene induction in macrophages

2000 • 301 citations

IL-12 Acts Directly on DC to Promote Nuclear Localization of NF-κB and Primes DC for IL-12 Production

1998 • 274 citations

Synergy of IL-12 and IL-18 for IFN-γ Gene Expression: IL-12-Induced STAT4 Contributes to IFN-γ Promoter Activation by Up-Regulating the Binding Activity of IL-18-Induced Activator Protein 1

2002 • 250 citations

Transcription

2002 • 241 citations

IL-23 and IL-12 Have Overlapping, but Distinct, Effects on Murine Dendritic Cells

2002 • 240 citations

Interferon Consensus Sequence Binding Protein–deficient Mice Display Impaired Resistance to Intracellular Infection Due to a Primary Defect in Interleukin 12 p40 Induction

1997 • 220 citations

Th1 and Th2 cells

2001 • 217 citations

Characterization of IL-12 receptor beta1 chain (IL-12Rbeta1)-deficient mice: IL-12Rbeta1 is an essential component of the functional mouse IL-12 receptor.

1997 • 211 citations

STAT4 serine phosphorylation is critical for IL-12-induced IFN-γ production but not for cell proliferation

2002 • 202 citations

The Production of IFN-γ by IL-12/IL-18-Activated Macrophages Requires STAT4 Signaling and Is Inhibited by IL-4

2001 • 195 citations

Inducible Expression of Stat4 in Dendritic Cells and Macrophages and Its Critical Role in Innate and Adaptive Immune Responses

2001 • 187 citations

An IFN-γ-Inducible Transcription Factor, IFN Consensus Sequence Binding Protein (ICSBP), Stimulates IL-12 p40 Expression in Macrophages

2000 • 185 citations

Differential regulation of interleukin-12 (IL-12), tumor necrosis factor alpha, and IL-1 beta production in human myeloid leukemia cell lines and peripheral blood mononuclear cells

1994 • 182 citations

Interleukin-12: a proinflammatory cytokine with immunoregulatory functions

1995 • 177 citations

Interferon (IFN) Consensus Sequence-binding Protein, a Transcription Factor of the IFN Regulatory Factor Family, Regulates Immune Responses In Vivo through Control of Interleukin 12 Expression

1997 • 164 citations

Activated STAT4 Has an Essential Role in Th1 Differentiation and Proliferation That Is Independent of Its Role in the Maintenance of IL-12Rβ2 Chain Expression and Signaling

2002 • 162 citations

IL-12 Receptor β2 (IL-12Rβ2)-Deficient Mice Are Defective in IL-12-Mediated Signaling Despite the Presence of High Affinity IL-12 Binding Sites

2000 • 161 citations

Cloning and characterization of a mouse IL-12 receptor-beta component.

1995 • 155 citations

T helper subset development: roles of instruction, selection, and transcription

2002 • 147 citations

SYNERGISTIC PROLIFERATION AND ACTIVATION OF NATURAL KILLER CELLS BY INTERLEUKIN 12 AND INTERLEUKIN 18

1999 • 147 citations

Regulation of the IL‐12/IL‐12R axis: a critical step in T‐helper cell differentiation and effector function

1999 • 146 citations

Identification and Characterization of a Novel Ets-2-related Nuclear Complex Implicated in the Activation of the Human Interleukin-12 p40 Gene Promoter

1997 • 143 citations

Differential Associations between the Cytoplasmic Regions of the Interleukin-12 Receptor Subunits β1 and β2 and JAK Kinases

1997 • 142 citations

The Functional Synergy Between IL-12 and IL-2 Involves p38 Mitogen-Activated Protein Kinase and Is Associated with the Augmentation of STAT Serine Phosphorylation

1999 • 142 citations

Antibodies to the IL-12 receptor beta 2 chain mark human Th1 but not Th2 cells in vitro and in vivo.

1999 • 140 citations

Interleukin‐12 Antagonist Activity of Mouse Interleukin‐12 p40 Homodimer in Vitro and in Vivo

1996 • 140 citations

IFN-γ Induces IL-12 mRNA Expression by a Murine Macrophage Cell Line, J774

1994 • 123 citations

Importance of the MKK6/p38 pathway for interleukin-12–induced STAT4 serine phosphorylation and transcriptional activity

2000 • 122 citations

T helper subset development: roles of instruction, selection, and transcription

2002 • 120 citations

The p38 Mitogen-Activated Protein Kinase Is Required for IL-12-Induced IFN-γ Expression

2000 • 118 citations

Antibodies to the IL-12 Receptor β2 Chain Mark Human Th1 But Not Th2 Cells In Vitro and In Vivo

1999 • 115 citations

Stat4 Regulates Multiple Components of IFN-γ-Inducing Signaling Pathways

2000 • 114 citations

IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice.

1999 • 113 citations

Interleukin-12: Basic Principles and Clinical Applications

1999 • 111 citations

Alloantigen-Reactive Th1 Development in IL-12-Deficient Mice

1998 • 110 citations

A Novel Function of IL-12p40 as a Chemotactic Molecule for Macrophages

1999 • 109 citations

IL-12 Is Dysregulated in Macrophages from IRF-1 and IRF-2 Knockout Mice

1999 • 104 citations

Synergistic Regulation of the Human Interleukin-12 p40 Promoter by NFκB and Ets Transcription Factors in Epstein-Barr Virus-transformed B Cells and Macrophages

1998 • 103 citations

Inherited disorders of IL-12- and IFNγ-mediated immunity: a molecular genetics update

2002 • 99 citations

Regulation of T cell-dependent and -independent IL-12 production by the three Th2-type cytokines IL-10, IL-6, and IL-4

1997 • 94 citations

Expression of Murine IL-12 Is Regulated by Translational Control of the p35 Subunit

1999 • 86 citations

IL-4 Pretreatment Selectively Enhances Cytokine and Chemokine Production in Lipopolysaccharide-Stimulated Mouse Peritoneal Macrophages

2002 • 77 citations

Contrasting roles of IL-12p40 and IL-12p35 in the development of hapten-induced colitis

2002 • 74 citations

An Absolute Requirement for STAT4 and a Role for IFN-γ as an Amplifying Factor in IL-12 Induction of the Functional IL-18 Receptor Complex

2001 • 72 citations

Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice

2002 • 70 citations

Cutting Edge: Differential Requirements for Stat4 in Expression of Glycosyltransferases Responsible for Selectin Ligand Formation in Th1 Cells

2001 • 66 citations

IL-12, STAT4-Dependent Up-Regulation of CD4+ T Cell Core 2 β-1,6-n-Acetylglucosaminyltransferase, an Enzyme Essential for Biosynthesis of P-Selectin Ligands

2001 • 66 citations

Identification of a STAT4 Binding Site in the Interleukin-12 Receptor Required for Signaling

1999 • 65 citations

Cytokine regulation of IL-12 receptor β2 expression: differential effects on human T and NK cells

2000 • 64 citations

T Helper Type 2 Cell Differentiation Occurs in the Presence of Interleukin 12 Receptor β2 Chain Expression and Signaling

2000 • 63 citations

Lineage commitment in lymphocytes: controlling the immune response.

2001 • 61 citations

IL-23: A Cytokine That Acts on Memory T Cells

2002 • 60 citations

Priming with IL-4 and IL-13 during HIV-1 infection restores in vitro IL-12 production by mononuclear cells of HIV-infected patients.

1997 • 46 citations

Reduced IFNγ production in response to IL‐12 stimulation and/or reduced IL‐12 production in atopic patients

2000 • 41 citations

BALB/c Mice Bearing a Transgenic IL-12 Receptor β2 Gene Exhibit a Nonhealing Phenotype toLeishmania majorInfection Despite Intact IL-12 Signaling

2001 • 38 citations

Phosphorylation of src Family lck Tyrosine Kinase Following Interleukin-12 Activation of Human Natural Killer Cells

1995 • 37 citations

A Mandatory Role for STAT4 in IL-12 Induction of Mouse T Cell CCR5

2001 • 35 citations

STAT4 serine phosphorylation is critical for IL-12- induced proliferation induced IFN-gamma production but not for cell proliferation

2002 • 27 citations

Atopy and mutations of IL‐12 receptor β2 chain gene

2001 • 18 citations

Positive and negative regulation of pathogen induced dendritic cell function by G-protein coupled receptors

2002 • 14 citations