Interleukin-21: basic biology and implications for cancer and autoimmunity.

Abstract:

:Interleukin-21 (IL-21), a potent immunomodulatory four-alpha-helical-bundle type I cytokine, is produced by NKT and CD4(+) T cells and has pleiotropic effects on both innate and adaptive immune responses. These actions include positive effects such as enhanced proliferation of lymphoid cells, increased cytotoxicity of CD8(+) T cells and natural killer (NK) cells, and differentiation of B cells into plasma cells. Conversely, IL-21 also has direct inhibitory effects on the antigen-presenting function of dendritic cells and can be proapoptotic for B cells and NK cells. IL-21 is also produced by Th17 cells and is a critical regulator of Th17 development. The regulatory activity of IL-21 is modulated by the differentiation state of its target cells as well as by other cytokines or costimulatory molecules. IL-21 has potent antitumor activity but is also associated with the development of autoimmune disease. IL-21 transcription is dependent on a calcium signal and NFAT sites, and IL-21 requires Stat3 for its signaling. The key to harnessing the power of IL-21 will depend on better understanding its range of biological actions, its mechanism of action, and the molecular basis of regulation of expression of IL-21 and its receptor.

journal_name

Annu Rev Immunol

authors

Spolski R,Leonard WJ

doi

10.1146/annurev.immunol.26.021607.090316

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

57-79

eissn

0732-0582

issn

1545-3278

journal_volume

26

pub_type

杂志文章,评审
  • Cellular basis of skin allograft rejection: an in vivo model of immune-mediated tissue destruction.

    abstract::Rejection of transplanted tissue allografts results from T-cell recognition of histocompatibility antigens expressed by cells of the donor graft. This review focuses on the phenotype, specificity, and function of the T cells mediating rejection responses against skin allografts, and on the immune mechanisms by which h...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.iy.10.040192.002001

    authors: Rosenberg AS,Singer A

    更新日期:1992-01-01 00:00:00

  • CD45: a critical regulator of signaling thresholds in immune cells.

    abstract::Regulation of tyrosine phosphorylation is a critical control point for integration of environmental signals into cellular responses. This regulation is mediated by the reciprocal actions of protein tyrosine kinases and phosphatases. CD45, the first and prototypic receptor-like protein tyrosine phosphatase, is expresse...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.21.120601.140946

    authors: Hermiston ML,Xu Z,Weiss A

    更新日期:2003-01-01 00:00:00

  • Genetic control of autoimmune diabetes in the NOD mouse.

    abstract::The nonobese diabetic (NOD) mouse is a model of human autoimmune insulin-dependent diabetes mellitus. The NOD mouse also serves as a model for studying complex polygenic diseases because at least fourteen different loci are linked to disease development. The first Idd locus recognized, Idd1, is linked to the major his...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.iy.13.040195.001143

    authors: Wicker LS,Todd JA,Peterson LB

    更新日期:1995-01-01 00:00:00

  • Siglecs as Immune Cell Checkpoints in Disease.

    abstract::Sialic acid-binding immunoglobulin-type lectins (Siglecs) are expressed on the majority of white blood cells of the immune system and play critical roles in immune cell signaling. Through recognition of sialic acid-containing glycans as ligands, they help the immune system distinguish between self and nonself. Because...

    journal_title:Annual review of immunology

    pub_type: 杂志文章

    doi:10.1146/annurev-immunol-102419-035900

    authors: Duan S,Paulson JC

    更新日期:2020-04-26 00:00:00

  • Chemokines and chemokine receptors: positioning cells for host defense and immunity.

    abstract::Chemokines are chemotactic cytokines that control the migratory patterns and positioning of all immune cells. Although chemokines were initially appreciated as important mediators of acute inflammation, we now know that this complex system of approximately 50 endogenous chemokine ligands and 20 G protein-coupled seven...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-immunol-032713-120145

    authors: Griffith JW,Sokol CL,Luster AD

    更新日期:2014-01-01 00:00:00

  • How neutrophils kill microbes.

    abstract::Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing, and digesting bacteria and fungi. Killing was previously believed to be accomplished by oxygen free radicals and other reactive oxygen species generated by the NADPH oxidase, and by oxidized halides produced by myelope...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.23.021704.115653

    authors: Segal AW

    更新日期:2005-01-01 00:00:00

  • The specificity and regulation of T-cell responsiveness to allergens.

    abstract::CD4+ T lymphocytes initiate and regulate both the specific and nonspecific effector mechanisms of allergic immune responses. The definition of immunogenic components within allergens has allowed the specificity of the T-cell repertoire to be examined, and the refinement of their molecular structure is now facilitating...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.iy.09.040191.000435

    authors: O'Hehir RE,Garman RD,Greenstein JL,Lamb JR

    更新日期:1991-01-01 00:00:00

  • Complement and the Regulation of T Cell Responses.

    abstract::The complement system is an evolutionarily ancient key component of innate immunity required for the detection and removal of invading pathogens. It was discovered more than 100 years ago and was originally defined as a liver-derived, blood-circulating sentinel system that classically mediates the opsonization and lyt...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-immunol-042617-053245

    authors: West EE,Kolev M,Kemper C

    更新日期:2018-04-26 00:00:00

  • Autophagy and the immune system.

    abstract::Stressors ranging from nutrient deprivation to immune signaling can induce the degradation of cytoplasmic material by a process known as autophagy. Increasingly, research on autophagy has begun to focus on its role in inflammation and the immune response. Autophagy acts as an immune effector that mediates pathogen cle...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-immunol-020711-074948

    authors: Kuballa P,Nolte WM,Castoreno AB,Xavier RJ

    更新日期:2012-01-01 00:00:00

  • TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation.

    abstract::Dendritic cells (DCs) are professional antigen-presenting cells that have the ability to sense infection and tissue stress, sample and present antigen to T lymphocytes, and induce different forms of immunity and tolerance. The functional versatility of DCs depends on their remarkable ability to translate collectively ...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.25.022106.141718

    authors: Liu YJ,Soumelis V,Watanabe N,Ito T,Wang YH,Malefyt Rde W,Omori M,Zhou B,Ziegler SF

    更新日期:2007-01-01 00:00:00

  • Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissues.

    abstract::Human immunodeficiency virus-1 (HIV-1) is usually transmitted through sexual contact and in the very early stages of infection establishes a persistent infection in lymphatic tissues (LT). Virus is produced and stored at this site in a dynamic process that slowly depletes the immune system of CD4+ T cells, setting the...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.17.1.625

    authors: Haase AT

    更新日期:1999-01-01 00:00:00

  • Natural suppressor (NS) cells, neonatal tolerance, and total lymphoid irradiation: exploring obscure relationships.

    abstract::Although several laboratories have shown that the appearance of naturally occurring suppressor cells in the spleens of neonatal or irradiated mice is temporarily related to the ease of induction of tolerance, the characteristics of these cells and their regulatory functions have been poorly understood until recently. ...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.iy.02.040184.001251

    authors: Strober S

    更新日期:1984-01-01 00:00:00

  • The IFN gamma receptor: a paradigm for cytokine receptor signaling.

    abstract::During the last several years, the mechanism of IFN gamma-dependent signal transduction has been the focus of intense investigation. This research has recently culminated in the elucidation of a comprehensive molecular understanding of the events that underlie IFN gamma-induced cellular responses. The structure and fu...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.15.1.563

    authors: Bach EA,Aguet M,Schreiber RD

    更新日期:1997-01-01 00:00:00

  • Function and activation of NF-kappa B in the immune system.

    abstract::NF-kappa B is a ubiquitous transcription factor. Nevertheless, its properties seem to be most extensively exploited in cells of the immune system. Among these properties are NF-kappa B's rapid posttranslational activation in response to many pathogenic signals, its direct participation in cytoplasmic/nuclear signaling...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.iy.12.040194.001041

    authors: Baeuerle PA,Henkel T

    更新日期:1994-01-01 00:00:00

  • Regulation and functions of the IL-10 family of cytokines in inflammation and disease.

    abstract::The IL-10 family of cytokines consists of nine members: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and the more distantly related IL-28A, IL-28B, and IL-29. Evolutionarily, IL-10 family cytokines emerged before the adaptive immune response. These cytokines elicit diverse host defense mechanisms, especially from epithel...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-immunol-031210-101312

    authors: Ouyang W,Rutz S,Crellin NK,Valdez PA,Hymowitz SG

    更新日期:2011-01-01 00:00:00

  • Translating molecular insights in autoimmunity into effective therapy.

    abstract::Autoimmunity and the pathogenesis of autoimmune diseases were a major focus of the Walter and Eliza Hall Institute, where I started my research career. After my initial studies on immune cell culture and immune regulation, I returned to an analysis of the pathogenesis of human autoimmunity in London. Linking upregulat...

    journal_title:Annual review of immunology

    pub_type: 传,历史文章,杂志文章

    doi:10.1146/annurev-immunol-082708-100732

    authors: Feldmann M

    更新日期:2009-01-01 00:00:00

  • The role of ThPOK in control of CD4/CD8 lineage commitment.

    abstract::During alphabeta T cell development, cells diverge into alternate CD4 helper and CD8(+) cytotoxic T cell lineages. The precise correlation between a T cell's CD8 and CD4 choice and its TCR specificity to class I or class II MHC was noted more than 20 years ago, and establishing the underlying mechanism has remained a ...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.25.022106.141715

    authors: He X,Park K,Kappes DJ

    更新日期:2010-01-01 00:00:00

  • Cross-presentation, dendritic cells, tolerance and immunity.

    abstract::This review examines the role of cross-presentation in tolerance and immunity. We discuss (a) the antigenic requirements for cross-presentation, (b) the phenotype of the antigen presenting cell (APC), (c) the cellular interactions and molecular signals involved in cross-priming, and (d) the factors that direct the imm...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.19.1.47

    authors: Heath WR,Carbone FR

    更新日期:2001-01-01 00:00:00

  • Ligand recognition by alpha beta T cell receptors.

    abstract::While still incomplete, the first data concerning the biochemistry of T cell receptor-ligand interactions in cell-free systems seem to have considerable predictive value regarding whether a T cell response is strong or weak or suppressive. This data will help considerably in elucidating the mechanisms behind T cell re...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.16.1.523

    authors: Davis MM,Boniface JJ,Reich Z,Lyons D,Hampl J,Arden B,Chien Y

    更新日期:1998-01-01 00:00:00

  • Using T Cell Receptor Repertoires to Understand the Principles of Adaptive Immune Recognition.

    abstract::Adaptive immune recognition is mediated by antigen receptors on B and T cells generated by somatic recombination during lineage development. The high level of diversity resulting from this process posed technical limitations that previously limited the comprehensive analysis of adaptive immune recognition. Advances ov...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-immunol-042718-041757

    authors: Bradley P,Thomas PG

    更新日期:2019-04-26 00:00:00

  • T cells as a self-referential, sensory organ.

    abstract::In light of recent data showing that both helper and cytotoxic T cells can detect even a single molecule of an agonist peptide-MHC, alphabeta T cells are clearly a type of sensory cell, comparable to any in the nervous system. In addition, endogenous (self) peptides bound to MHCs are not just important for thymic sele...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.24.021605.090600

    authors: Davis MM,Krogsgaard M,Huse M,Huppa J,Lillemeier BF,Li QJ

    更新日期:2007-01-01 00:00:00

  • CD8+ T cell effector mechanisms in resistance to infection.

    abstract::Based on T cell subset depletion studies and the analysis of gene knockout mice, it is evident that CD8(+) T cells contribute to resistance against intracellular infections with certain viral, protozoan, and bacterial pathogens. Although they are known primarily for their capacity to kill infected cells, CD8(+) T cell...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.18.1.275

    authors: Harty JT,Tvinnereim AR,White DW

    更新日期:2000-01-01 00:00:00

  • Regulation and function of NF-kappaB transcription factors in the immune system.

    abstract::The mammalian Rel/NF-kappaB family of transcription factors, including RelA, c-Rel, RelB, NF-kappaB1 (p50 and its precursor p105), and NF-kappaB2 (p52 and its precursor p100), plays a central role in the immune system by regulating several processes ranging from the development and survival of lymphocytes and lymphoid...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.021908.132641

    authors: Vallabhapurapu S,Karin M

    更新日期:2009-01-01 00:00:00

  • Tolerance of infections.

    abstract::A host has two methods to defend against pathogens: It can clear the pathogens or reduce their impact on health in other ways. The first, resistance, is well studied. Study of the second, which ecologists call tolerance, is in its infancy. Tolerance measures the dose response curve of a host's health in reaction to a ...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-immunol-020711-075030

    authors: Ayres JS,Schneider DS

    更新日期:2012-01-01 00:00:00

  • Genetic analysis of tyrosine kinase function in B cell development.

    abstract::B lymphopoiesis is regulated by multiple signals from stromal cell contact, soluble cytokines, antigen, and T helper cells. In vitro and biochemical experiments have implicated tyrosine kinases as key components of many of these signaling pathways. Genetic analysis of the role of these tyrosine kinases has been facili...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.14.1.131

    authors: Satterthwaite A,Witte O

    更新日期:1996-01-01 00:00:00

  • Altering genes in animals by gene targeting.

    abstract::It is possible to create mice in which a planned alteration has been introduced at a specific locus in the genome. The planned alteration is first introduced into the genome of mouse embryonic stem (ES) cells in tissue culture. This is accomplished by homologous recombination between the targeted genomic locus and DNA...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.iy.10.040192.003421

    authors: Koller BH,Smithies O

    更新日期:1992-01-01 00:00:00

  • Properties of the novel proinflammatory supergene "intercrine" cytokine family.

    abstract::A family consisting of at least ten distinct novel 8-10 kd cytokines has been identified over the past 12 years. These cytokines exhibit from 20 to 45% homology in amino acid sequence, are probably all basic heparin-binding polypeptides, and have proinflammatory and reparative activities. The cDNA for these cytokines ...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.iy.09.040191.003153

    authors: Oppenheim JJ,Zachariae CO,Mukaida N,Matsushima K

    更新日期:1991-01-01 00:00:00

  • Transcriptional control of early T and B cell developmental choices.

    abstract::T and B cells share a common somatic gene rearrangement mechanism for assembling the genes that code for their antigen receptors; they also have developmental pathways with many parallels. Shared usage of basic helix-loop-helix E proteins as transcriptional drivers underlies these common features. However, the transcr...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev-immunol-032712-100024

    authors: Rothenberg EV

    更新日期:2014-01-01 00:00:00

  • On natural and artificial vaccinations.

    abstract::This review summarizes the general parameters of cell- and antibody-mediated immune protection and the basic mechanisms responsible for what we call immunological memory. From this basis, the various successes and difficulties of vaccines are evaluated with respect to the role of antigen in maintaining protective immu...

    journal_title:Annual review of immunology

    pub_type: 杂志文章,评审

    doi:10.1146/annurev.immunol.21.120601.141045

    authors: Zinkernagel RM

    更新日期:2003-01-01 00:00:00

  • Neuroendocrine regulation of immunity.

    abstract::A reciprocal regulation exists between the central nervous and immune systems through which the CNS signals the immune system via hormonal and neuronal pathways and the immune system signals the CNS through cytokines. The primary hormonal pathway by which the CNS regulates the immune system is the hypothalamic-pituita...

    journal_title:Annual review of immunology

    pub_type: 杂志文章

    doi:10.1146/annurev.immunol.20.082401.104914

    authors: Webster JI,Tonelli L,Sternberg EM

    更新日期:2002-01-01 00:00:00