(Q38206058)

31 August 2017

title

Interleukin-21: a double-edged sword with therapeutic potential (English)

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31 August 2017

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Rosanne Spolski

1

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31 August 2017

Warren J Leonard

series ordinal

2

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31 August 2017

publication date

22 April 2014

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Nature Reviews Drug Discovery

31 August 2017

published in

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31 August 2017

volume

13

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31 August 2017

issue

5

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31 August 2017

page(s)

379-395

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Interleukin-21: Basic Biology and Implications for Cancer and Autoimmunity

31 August 2017

cites work

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Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function

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Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain

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Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex

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Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans

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Cytokines and immunodeficiency diseases

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Rational design of interleukin-21 antagonist through selective elimination of the gammaC binding epitope

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The molecular basis of IL-21-mediated proliferation

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Analysis of interleukin-21-induced Prdm1 gene regulation reveals functional cooperation of STAT3 and IRF4 transcription factors

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BATF-JUN is critical for IRF4-mediated transcription in T cells

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A validated regulatory network for Th17 cell specification

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A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes

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Targeting the Janus kinases in rheumatoid arthritis: focus on tofacitinib

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Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis.

21 January 2018

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A critical role for IL-21 in regulating immunoglobulin production

21 January 2018

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IL-21 is the primary common γ chain-binding cytokine required for human B-cell differentiation in vivo

21 January 2018

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Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells

21 January 2018

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IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells.

21 January 2018

1 reference

IL-21-induced isotype switching to IgG and IgA by human naive B cells is differentially regulated by IL-4.

21 January 2018

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Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells.

21 January 2018

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A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts

21 January 2018

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Distinct activation signals determine whether IL-21 induces B cell costimulation, growth arrest, or Bim-dependent apoptosis

21 January 2018

1 reference

Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6

21 January 2018

1 reference

Regulatory mechanisms that determine the development and function of plasma cells

21 January 2018

1 reference

STAT3-mediated up-regulation of BLIMP1 Is coordinated with BCL6 down-regulation to control human plasma cell differentiation.

21 January 2018

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B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans

21 January 2018

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Activated Mouse B Cells Lack Expression of Granzyme B

21 January 2018

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Human plasma cells express granzyme B.

21 January 2018

1 reference

Interleukin-21 inhibits dendritic cell activation and maturation

21 January 2018

1 reference

The cytokines IL-21 and GM-CSF have opposing regulatory roles in the apoptosis of conventional dendritic cells

21 January 2018

1 reference

Targeting IL-17 and TH17 cells in chronic inflammation

21 January 2018

1 reference

IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells

21 January 2018

1 reference

Essential autocrine regulation by IL-21 in the generation of inflammatory T cells

21 January 2018

1 reference

IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways

21 January 2018

1 reference

Transcriptional regulation of Th17 cell differentiation

21 January 2018

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IL-21 and IL-21R are not required for development of Th17 cells and autoimmunity in vivo

21 January 2018

1 reference

The good, the bad and the ugly - TFH cells in human health and disease

21 January 2018

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T follicular helper (TFH) cells in normal and dysregulated immune responses

21 January 2018

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IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses

21 January 2018

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IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism

21 January 2018

1 reference

The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells

21 January 2018

1 reference

Bcl6 mediates the development of T follicular helper cells

21 January 2018

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The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment.

21 January 2018

1 reference

IL-21 and IL-6 are critical for different aspects of B cell immunity and redundantly induce optimal follicular helper CD4 T cell (Tfh) differentiation

21 January 2018

1 reference

The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by CD4+ T cells

21 January 2018

1 reference

A Nonredundant Role for IL-21 Receptor Signaling in Plasma Cell Differentiation and Protective Type 2 Immunity against Gastrointestinal Helminth Infection

21 January 2018

1 reference

Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells.

21 January 2018

1 reference

The development and fate of follicular helper T cells defined by an IL-21 reporter mouse

21 January 2018

1 reference

Cytokine-secreting follicular T cells shape the antibody repertoire

21 January 2018

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Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion

21 January 2018

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Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation

21 January 2018

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Plasma cells negatively regulate the follicular helper T cell program

21 January 2018

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Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions

21 January 2018

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Foxp3+ follicular regulatory T cells control the germinal center response.

21 January 2018

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Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine

21 January 2018

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IL-21 inhibits T cell IL-2 production and impairs Treg homeostasis.

21 January 2018

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IL-21 restricts virus-driven Treg cell expansion in chronic LCMV infection.

21 January 2018

1 reference

IL-21 contributes to fatal inflammatory disease in the absence of Foxp3+ T regulatory cells.

21 January 2018

1 reference

IL-21 mediates suppressive effects via its induction of IL-10.

21 January 2018

1 reference

Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells

21 January 2018

1 reference

Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function.

21 January 2018

1 reference

IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy

21 January 2018

1 reference

Interleukin-21-producing HIV-1-specific CD8 T cells are preferentially seen in elite controllers

21 January 2018

1 reference

Inborn errors of human JAKs and STATs

21 January 2018

1 reference

Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome

21 January 2018

1 reference

STAT3 mutations in the hyper-IgE syndrome

21 January 2018

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Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome

21 January 2018

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Signal transducer and activator of transcription 3 (STAT3) mutations underlying autosomal dominant hyper-IgE syndrome impair human CD8(+) T-cell memory formation and function.

21 January 2018

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Functional STAT3 deficiency compromises the generation of human T follicular helper cells.

21 January 2018

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Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome

21 January 2018

1 reference

A critical role for STAT3 transcription factor signaling in the development and maintenance of human T cell memory

21 January 2018

1 reference

The IL-21 receptor augments Th2 effector function and alternative macrophage activation

21 January 2018

1 reference

Interleukin 21: combination strategies for cancer therapy

21 January 2018

1 reference

IL-21 enhances tumor rejection through a NKG2D-dependent mechanism

21 January 2018

1 reference

IL-21 enhances and sustains CD8+ T cell responses to achieve durable tumor immunity: comparative evaluation of IL-2, IL-15, and IL-21

21 January 2018

1 reference

Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy

21 January 2018

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Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells

21 January 2018

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IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients

21 January 2018

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IL-21 promotes the expansion of CD27+ CD28+ tumor infiltrating lymphocytes with high cytotoxic potential and low collateral expansion of regulatory T cells.

21 January 2018

1 reference

Paths to stemness: building the ultimate antitumour T cell.

21 January 2018

1 reference

Interleukin-21 enhances NK cell activation in response to antibody-coated targets

21 January 2018

1 reference

Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy

21 January 2018

1 reference

Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer

21 January 2018

1 reference

Combined IL-21 and low-dose IL-2 therapy induces anti-tumor immunity and long-term curative effects in a murine melanoma tumor model

21 January 2018

1 reference

Interleukin (IL)-21 and IL-15 genetic transfer synergistically augments therapeutic antitumor immunity and promotes regression of metastatic lymphoma.

21 January 2018

1 reference

Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage IV malignant melanoma without prior treatment: a phase IIa trial.

21 January 2018

1 reference

A phase 1 trial of recombinant human IL-21 in combination with cetuximab in patients with metastatic colorectal cancer

21 January 2018

1 reference

Involvement of interleukin-21 in the regulation of colitis-associated colon cancer

21 January 2018

1 reference

IL-21 mediates apoptosis through up-regulation of the BH3 family member BIM and enhances both direct and antibody-dependent cellular cytotoxicity in primary chronic lymphocytic leukemia cells in vitro

21 January 2018

1 reference

Differential regulation of B-cell proliferation by IL21 in different subsets of chronic lymphocytic leukemia.

21 January 2018

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B-chronic lymphocytic leukemia cells and other B cells can produce granzyme B and gain cytotoxic potential after interleukin-21-based activation.

21 January 2018

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Enhancement of CD154/IL4 proliferation by the T follicular helper (Tfh) cytokine, IL21 and increased numbers of circulating cells resembling Tfh cells in chronic lymphocytic leukaemia.

21 January 2018

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IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells.

21 January 2018

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Novel IL-21 signaling pathway up-regulates c-Myc and induces apoptosis of diffuse large B-cell lymphomas.

21 January 2018

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Abundant expression of interleukin-21 receptor in follicular lymphoma cells is associated with more aggressive disease

21 January 2018

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High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma

21 January 2018

1 reference

Heterogeneous expression and function of IL-21R and susceptibility to IL-21-mediated apoptosis in follicular lymphoma cells

21 January 2018

1 reference

A unifying microenvironment model in follicular lymphoma: outcome is predicted by programmed death-1--positive, regulatory, cytotoxic, and helper T cells and macrophages

21 January 2018

1 reference

Interleukin-21 is a growth and survival factor for human myeloma cells

21 January 2018

1 reference

IL-21 stimulates human myeloma cell growth through an autocrine IGF-1 loop

21 January 2018

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IL-21 is expressed in Hodgkin lymphoma and activates STAT5: evidence that activated STAT5 is required for Hodgkin lymphomagenesis

21 January 2018

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Angioimmunoblastic T-cell lymphoma.

21 January 2018

1 reference

The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells

21 January 2018

1 reference

Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma

21 January 2018

1 reference

Angioimmunoblastic T-cell lymphoma: a neoplasm of germinal-center T-helper cells?

21 January 2018

1 reference

The inducible T-cell co-stimulator molecule is expressed on subsets of T cells and is a new marker of lymphomas of T follicular helper cell-derivation

21 January 2018

1 reference

Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human

21 January 2018

1 reference

Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma

21 January 2018

1 reference

A phase I dose-finding trial of recombinant interleukin-21 and rituximab in relapsed and refractory low grade B-cell lymphoproliferative disorders

21 January 2018

1 reference

Intrinsic IL-21 signaling is critical for CD8 T cell survival and memory formation in response to vaccinia viral infection

21 January 2018

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IL-21R on T cells is critical for sustained functionality and control of chronic viral infection

21 January 2018

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IL-21 is required to control chronic viral infection

21 January 2018

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A vital role for interleukin-21 in the control of a chronic viral infection

21 January 2018

1 reference

IL-21 Deficiency Influences CD8 T Cell Quality and Recall Responses following an Acute Viral Infection

21 January 2018

1 reference

An interleukin-21-interleukin-10-STAT3 pathway is critical for functional maturation of memory CD8+ T cells

21 January 2018

1 reference

HBcAg-specific IL-21-producing CD4+ T cells are associated with relative viral control in patients with chronic hepatitis B.

21 January 2018

1 reference

IL-21 is pivotal in determining age-dependent effectiveness of immune responses in a mouse model of human hepatitis B.

21 January 2018

1 reference

Age-dependent hepatic lymphoid organization directs successful immunity to hepatitis B.

21 January 2018

1 reference

Galectin-9 and IL-21 mediate cross-regulation between Th17 and Treg cells during acute hepatitis C.

21 January 2018

1 reference

Dynamics and consequences of IL-21 production in HIV-infected individuals: a longitudinal and cross-sectional study.

21 January 2018

1 reference

HIV-specific IL-21 producing CD4+ T cells are induced in acute and chronic progressive HIV infection and are associated with relative viral control.

21 January 2018

1 reference

HIV-1-specific interleukin-21+ CD4+ T cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T cell function

21 January 2018

1 reference

Differential effects of IL-21 and IL-15 on perforin expression, lysosomal degranulation, and proliferation in CD8 T cells of patients with human immunodeficiency virus-1 (HIV)

21 January 2018

1 reference

Expansion of HIV-specific T follicular helper cells in chronic HIV infection

21 January 2018

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Inadequate T follicular cell help impairs B cell immunity during HIV infection.

21 January 2018

1 reference

Interleukin-21 administration to rhesus macaques chronically infected with simian immunodeficiency virus increases cytotoxic effector molecules in T cells and NK cells and enhances B cell function without increasing immune activation or viral replic

21 January 2018

1 reference

Maintenance of intestinal Th17 cells and reduced microbial translocation in SIV-infected rhesus macaques treated with interleukin (IL)-21

21 January 2018

1 reference

IL-21 promotes the pathologic immune response to pneumovirus infection.

21 January 2018

1 reference

Fine-mapping and transethnic genotyping establish IL2/IL21 genetic association with lupus and localize this genetic effect to IL21

21 January 2018

1 reference

Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci

21 January 2018

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Novel association of the interleukin 2-interleukin 21 region with inflammatory bowel disease.

21 January 2018

1 reference

A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21

21 January 2018

1 reference

A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci

21 January 2018

1 reference

IL-21 is a double-edged sword in the systemic lupus erythematosus-like disease of BXSB.Yaa mice

21 January 2018

1 reference

A critical role for IL-21 receptor signaling in the pathogenesis of systemic lupus erythematosus in BXSB-Yaa mice

21 January 2018

1 reference

IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression.

21 January 2018

1 reference

Interleukin 21 correlates with T cell and B cell subset alterations in systemic lupus erythematosus.

21 January 2018

1 reference

A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25- T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice.

21 January 2018

1 reference

Increased frequency of circulating follicular helper T cells in patients with rheumatoid arthritis

21 January 2018

1 reference

The cellular source and target of IL-21 in K/BxN autoimmune arthritis

21 January 2018

1 reference

Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial

21 January 2018

1 reference

Interleukin-6 receptor blockade selectively reduces IL-21 production by CD4 T cells and IgG4 autoantibodies in rheumatoid arthritis

21 January 2018

1 reference

Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis.

21 January 2018

1 reference

Homeostatic expansion of T cells during immune insufficiency generates autoimmunity.

21 January 2018

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IL-21 signaling is critical for the development of type I diabetes in the NOD mouse

21 January 2018

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Interleukin-21 is required for the development of type 1 diabetes in NOD mice

21 January 2018

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Differential IL-21 signaling in APCs leads to disparate Th17 differentiation in diabetes-susceptible NOD and diabetes-resistant NOD.Idd3 mice.

21 January 2018

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Interleukin-21 receptor-mediated signals control autoreactive T cell infiltration in pancreatic islets

21 January 2018

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Exposure to IL-15 and IL-21 enables autoreactive CD8 T cells to respond to weak antigens and cause disease in a mouse model of autoimmune diabetes.

21 January 2018

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Interleukin-21 is critically required in autoimmune and allogeneic responses to islet tissue in murine models.

21 January 2018

1 reference

RGMA and IL21R show association with experimental inflammation and multiple sclerosis

21 January 2018

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IL-21 and IL-21 receptor expression in lymphocytes and neurons in multiple sclerosis brain

21 January 2018

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Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17- and activated B-cells and correlates with progression

21 January 2018

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Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions.

21 January 2018

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Key role for IL-21 in experimental autoimmune uveitis

21 January 2018

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The immunological and genetic basis of inflammatory bowel disease

21 January 2018

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IL-21 comes of age as a regulator of effector T cells in the gut.

21 January 2018

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Interleukin-21 enhances T-helper cell type I signaling and interferon-gamma production in Crohn's disease

21 January 2018

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Regulation of gut inflammation and th17 cell response by interleukin-21.

21 January 2018

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Control of matrix metalloproteinase production in human intestinal fibroblasts by interleukin 21.

21 January 2018

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IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo

21 January 2018

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IL-21 administration into the nostril alleviates murine allergic rhinitis

21 January 2018

1 reference

An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma

21 January 2018

1 reference

Interleukin-21 has activity in patients with metastatic melanoma: a phase II study

21 January 2018

1 reference

A phase I study of recombinant human interleukin-21 (rIL-21) in combination with sunitinib in patients with metastatic renal cell carcinoma (RCC).

21 January 2018

1 reference

Recombinant interleukin-21 plus sorafenib for metastatic renal cell carcinoma: a phase 1/2 study

21 January 2018

1 reference

Anti-IL21 receptor monoclonal antibody (ATR-107): Safety, pharmacokinetics, and pharmacodynamic evaluation in healthy volunteers: a phase I, first-in-human study

21 January 2018

1 reference

Treatment of BXSB-Yaa mice with IL-21R-Fc fusion protein minimally attenuates systemic lupus erythematosus.

21 January 2018

1 reference

Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis

21 January 2018

1 reference

IL-21 induces the apoptosis of resting and activated primary B cells

21 January 2018

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Cutting edge: IL-21 derived from human follicular helper T cells acts as a survival factor for secondary lymphoid organ, but not for bone marrow, plasma cells

31 March 2020

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Human B cells differentiate into granzyme B-secreting cytotoxic B lymphocytes upon incomplete T-cell help

31 March 2020

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Cutting Edge: IL-21 Is Not Essential for Th17 Differentiation or Experimental Autoimmune Encephalomyelitis

31 March 2020

1 reference

A Subset of Interleukin-21+ Chemokine Receptor CCR9+ T Helper Cells Target Accessory Organs of the Digestive System in Autoimmunity

31 March 2020

1 reference

IL-27 induction of IL-21 from human CD8+ T cells induces granzyme B in an autocrine manner

31 March 2020

1 reference

Phase I study of recombinant interleukin-21 in patients with metastatic melanoma and renal cell carcinoma

31 March 2020

1 reference

Clinicopathologic analysis of peripheral T-cell lymphoma, follicular variant, and comparison with angioimmunoblastic T-cell lymphoma: Bcl-6 expression might affect progression between these disorders

31 March 2020

1 reference

Interleukin-21 is upregulated in hepatitis B-related acute-on-chronic liver failure and associated with severity of liver disease

31 March 2020

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High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B

31 March 2020

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Interleukin-21 mediates hepatitis B virus-associated liver cirrhosis by activating hepatic stellate cells

31 March 2020

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IL-21 regulates Th17 cells in rheumatoid arthritis

31 March 2020

1 reference

Differential effects of IL-21 during initiation and progression of autoimmunity against neuroantigen

31 March 2020

1 reference

Increased production of interleukin-21, but not interleukin-17A, in the small intestine characterizes pediatric celiac disease

31 March 2020

1 reference

A Functional Role for Interleukin-21 in Promoting the Synthesis of the T-Cell Chemoattractant, MIP-3α, by Gut Epithelial Cells

31 March 2020

1 reference

Interleukin 21 controls tumour growth and tumour immunosurveillance in colitis-associated tumorigenesis in mice

31 March 2020

1 reference

Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line C(epsilon) transcription of IL-4-stimulated B cells

31 March 2020

1 reference

IL-21 reduces immediate hypersensitivity reactions in mouse skin by suppressing mast cell activation or IgE production

31 March 2020

1 reference

In vivo antitumor activity of interleukin 21 mediated by natural killer cells

31 March 2020

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12 December 2020

Comparison of vascular leak syndrome in mice treated with IL21 or IL2

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12 December 2020

IL-21R is essential for epicutaneous sensitization and allergic skin inflammation in humans and mice.

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12 December 2020

IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H)

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12 December 2020

Identifiers

DOI

10.1038/NRD4296

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31 August 2017

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