当前位置： SCI文献检索 > IMMUNITY期刊下所有文献 > Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4+ T Cell Dysfunction.

Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4+ T Cell Dysfunction.

Abstract：

:CD4+ T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplantation. IRF4 deletion in mice resulted in progressive establishment of CD4+ T cell dysfunction and long-term allograft survival. Mechanistically, IRF4 repressed PD-1, Helios, and other molecules associated with T cell dysfunction. In the absence of IRF4, chromatin accessibility and binding of Helios at PD-1 cis-regulatory elements were increased, resulting in enhanced PD-1 expression and CD4+ T cell dysfunction. The dysfunctional state of Irf4-deficient T cells was initially reversible by PD-1 ligand blockade, but it progressively developed into an irreversible state. Hence, IRF4 controls a core regulatory circuit of CD4+ T cell dysfunction, and targeting IRF4 represents a potential therapeutic strategy for achieving transplant acceptance.

journal_name

Immunity

journal_title

Immunity

authors

Wu J,Zhang H,Shi X,Xiao X,Fan Y,Minze LJ,Wang J,Ghobrial RM,Xia J,Sciammas R,Li XC,Chen W

doi

10.1016/j.immuni.2017.11.003

subject

Has Abstract

pub_date

2017-12-19 00:00:00

pages

1114-1128.e6

issue

6

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(17)30480-6

journal_volume

47

pub_type

杂志文章

相关文献

IMMUNITY文献大全
  • In vitro generation of lymphohematopoietic cells from endothelial cells purified from murine embryos.

    abstract：:We have investigated the lymphohematopoietic potentials of endothelial cells (EC) and hematopoietic cells (HPC) sorted from embryos. Expression of VE-cadherin, CD45, and Ter119 was used to distinguish EC (VE-cadherin+CD45-Ter119-) from HPC (VE-cadherin-CD45+). Thus defined, EC population takes up acetylated LDL and co...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/s1074-7613(00)80581-6

    authors： Nishikawa SI,Nishikawa S,Kawamoto H,Yoshida H,Kizumoto M,Kataoka H,Katsura Y

    更新日期：1998-06-01 00:00:00

  • Myelopoiesis Reloaded: Single-Cell Transcriptomics Leads the Way.

    abstract：:Lineage commitment during myelopoiesis has been linked to late-stage progenitors with multi-lineage potential. In a recent issue of Cell, Paul et al. (2015) now suggest a much earlier commitment toward distinct lineages even prior to the common myeloid progenitor state. ...

    journal_title：Immunity

    pub_type： 评论,杂志文章

    doi：10.1016/j.immuni.2015.12.019

    authors： Schultze JL,Beyer M

    更新日期：2016-01-19 00:00:00

  • F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells.

    abstract：:Sterile inflammation can be initiated by innate immune recognition of markers of tissue injury termed damage-associated molecular patterns (DAMPs). DAMP recognition by dendritic cells (DCs) has also been postulated to lead to T cell responses to foreign antigens in tumors or allografts. Many DAMPs represent intracellu...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2012.03.008

    authors： Ahrens S,Zelenay S,Sancho D,Hanč P,Kjær S,Feest C,Fletcher G,Durkin C,Postigo A,Skehel M,Batista F,Thompson B,Way M,Reis e Sousa C,Schulz O

    更新日期：2012-04-20 00:00:00

  • Aiolos: an ungrateful member of the Ikaros family.

    abstract：:Ikaros family members play an important role in hematopoietic development. Thompson et al. (2007) show that pre-BCR signaling induces Aiolos expression, which in turn suppresses the expression of the pre-BCR component lambda5 and eliminates the very structure that signaled its appearance. ...

    journal_title：Immunity

    pub_type： 评论,杂志文章,评审

    doi：10.1016/j.immuni.2007.03.003

    authors： Kioussis D

    更新日期：2007-03-01 00:00:00

  • Determination of the HLA-DM interaction site on HLA-DR molecules.

    abstract：:HLA-DM removes CLIP and other loosely bound peptides from MHC class II molecules. The crystal structures of class II molecules and of HLA-DM have not permitted identification of their interaction sites. Here, we describe mutations in class II that impair interactions with DM. Libraries of randomly mutagenized DR3 alph...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/s1074-7613(00)00051-0

    authors： Doebele RC,Busch R,Scott HM,Pashine A,Mellins ED

    更新日期：2000-10-01 00:00:00

  • Dynamic actin polymerization drives T cell receptor-induced spreading: a role for the signal transduction adaptor LAT.

    abstract：:T cell activation induces functional changes in cell shape and cytoskeletal architecture. To facilitate the collection of dynamic, high-resolution images of activated T cells, we plated T cells on coverslips coated with antibodies to the T cell receptor (TCR). Using these images, we were able to quantitate the morphol...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/s1074-7613(01)00112-1

    authors： Bunnell SC,Kapoor V,Trible RP,Zhang W,Samelson LE

    更新日期：2001-03-01 00:00:00

  • Monocytes Take Their Own Path to IL-1β.

    abstract：:Generally, two signals are required to activate the NLRP3 inflammasome. In this issue of Immunity, Hornung and colleagues (2016) describe an alternative inflammasome activation pathway in human monocytes triggering activation of the NLRP3 inflammasome in response to a single stimulus. ...

    journal_title：Immunity

    pub_type： 评论,杂志文章

    doi：10.1016/j.immuni.2016.03.015

    authors： Elliott EI,Sutterwala FS

    更新日期：2016-04-19 00:00:00

  • Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis.

    abstract：:PKCβ-null (Prkcb-/-) mice are severely immunodeficient. Here we show that mice whose B cells lack PKCβ failed to form germinal centers and plasma cells, which undermined affinity maturation and antibody production in response to immunization. Moreover, these mice failed to develop plasma cells in response to viral inf...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2018.04.031

    authors： Tsui C,Martinez-Martin N,Gaya M,Maldonado P,Llorian M,Legrave NM,Rossi M,MacRae JI,Cameron AJ,Parker PJ,Leitges M,Bruckbauer A,Batista FD

    更新日期：2018-06-19 00:00:00

  • MHC Class II Antigen Presentation by the Intestinal Epithelium Initiates Graft-versus-Host Disease and Is Influenced by the Microbiota.

    abstract：:Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract is the principal determinant of lethality following allogeneic bone marrow transplantation (BMT). Here, we examined the mechanisms that initiate GVHD, including the relevant antigen-presenting cells. MHC class II was expressed on intestinal epithelial...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2019.08.011

    authors： Koyama M,Mukhopadhyay P,Schuster IS,Henden AS,Hülsdünker J,Varelias A,Vetizou M,Kuns RD,Robb RJ,Zhang P,Blazar BR,Thomas R,Begun J,Waddell N,Trinchieri G,Zeiser R,Clouston AD,Degli-Esposti MA,Hill GR

    更新日期：2019-11-19 00:00:00

  • Regulatory T cells and inflammation: better late than never.

    abstract：:In this issue of Immunity, Curotto de Lafaille et al. (2008) show that adaptive T regulatory cells control airway inflammation and that it is when they are generated that determines whether they function during acute or chronic inflammation. ...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2008.07.001

    authors： Ziegler SF

    更新日期：2008-07-18 00:00:00

  • Impaired Kupffer Cell Self-Renewal Alters the Liver Response to Lipid Overload during Non-alcoholic Steatohepatitis.

    abstract：:Kupffer cells (KCs) are liver-resident macrophages that self-renew by proliferation in the adult independently from monocytes. However, how they are maintained during non-alcoholic steatohepatitis (NASH) remains ill defined. We found that a fraction of KCs derived from Ly-6C+ monocytes during NASH, underlying impaired...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2020.06.003

    authors： Tran S,Baba I,Poupel L,Dussaud S,Moreau M,Gélineau A,Marcelin G,Magréau-Davy E,Ouhachi M,Lesnik P,Boissonnas A,Le Goff W,Clausen BE,Yvan-Charvet L,Sennlaub F,Huby T,Gautier EL

    更新日期：2020-09-15 00:00:00

  • Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production.

    abstract：:Pancreatic-islet inflammation contributes to the failure of β cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and e...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2017.10.015

    authors： Dalmas E,Lehmann FM,Dror E,Wueest S,Thienel C,Borsigova M,Stawiski M,Traunecker E,Lucchini FC,Dapito DH,Kallert SM,Guigas B,Pattou F,Kerr-Conte J,Maechler P,Girard JP,Konrad D,Wolfrum C,Böni-Schnetzler M,Finke D,D

    更新日期：2017-11-21 00:00:00

  • SHP-2 phosphatase negatively regulates the TRIF adaptor protein-dependent type I interferon and proinflammatory cytokine production.

    abstract：:The Toll-like receptor 3 (TLR3) and TLR4-signaling pathway that involves the adaptor protein TRIF activates type I interferon (IFN) and proinflammatory cytokine expression. Little is known about how TRIF pathway-dependent gene expression is regulated. SH2-containing protein tyrosine phosphatase 2 (SHP-2) is a widely e...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2006.10.014

    authors： An H,Zhao W,Hou J,Zhang Y,Xie Y,Zheng Y,Xu H,Qian C,Zhou J,Yu Y,Liu S,Feng G,Cao X

    更新日期：2006-12-01 00:00:00

  • Analysis of a SARS-CoV-2-Infected Individual Reveals Development of Potent Neutralizing Antibodies with Limited Somatic Mutation.

    abstract：:Antibody responses develop following SARS-CoV-2 infection, but little is known about their epitope specificities, clonality, binding affinities, epitopes, and neutralizing activity. We isolated B cells specific for the SARS-CoV-2 envelope glycoprotein spike (S) from a COVID-19-infected subject 21 days after the onset ...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2020.06.001

    authors： Seydoux E,Homad LJ,MacCamy AJ,Parks KR,Hurlburt NK,Jennewein MF,Akins NR,Stuart AB,Wan YH,Feng J,Whaley RE,Singh S,Boeckh M,Cohen KW,McElrath MJ,Englund JA,Chu HY,Pancera M,McGuire AT,Stamatatos L

    更新日期：2020-07-14 00:00:00

  • Antigen presentation in extracellular matrix: interactions of T cells with dendritic cells are dynamic, short lived, and sequential.

    abstract：:Cognate interactions of naive T cells with antigen-presenting dendritic cells require physical cell-cell contacts leading to signal induction and T cell activation. Using a three-dimensional collagen matrix videomicroscopy model for ovalbumin peptide-specific activation of murine and oxidative mitogenesis of human T c...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/s1074-7613(00)00032-7

    authors： Gunzer M,Schäfer A,Borgmann S,Grabbe S,Zänker KS,Bröcker EB,Kämpgen E,Friedl P

    更新日期：2000-09-01 00:00:00

  • The COVID-19 Serology Studies Workshop: Recommendations and Challenges.

    abstract：:The development, validation, and appropriate application of serological assays to detect antibodies to SARS-CoV-2 are essential to determining seroprevalence of this virus in the United States and globally and in guiding government leadership and the private sector on back-to-work policies. An interagency working grou...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2020.06.012

    authors： Lerner AM,Eisinger RW,Lowy DR,Petersen LR,Humes R,Hepburn M,Cassetti MC

    更新日期：2020-07-14 00:00:00

  • Bacterial infections promote T cell recognition of self-glycolipids.

    abstract：:Recognition of self is essential for repertoire selection, immune regulation, and autoimmunity and may be a consequence of infection. Self-induced recognition may represent the escape mechanism adopted by pathogens but may also incite autoimmune diseases. Here, we show that bacterial infection may promote activation o...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2005.04.013

    authors： De Libero G,Moran AP,Gober HJ,Rossy E,Shamshiev A,Chelnokova O,Mazorra Z,Vendetti S,Sacchi A,Prendergast MM,Sansano S,Tonevitsky A,Landmann R,Mori L

    更新日期：2005-06-01 00:00:00

  • TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells.

    abstract：:We describe de novo generation of IL-17-producing T cells from naive CD4 T cells, induced in cocultures of naive CD4 T cells and naturally occurring CD4+ CD25+ T cells (Treg) in the presence of TLR3, TLR4, or TLR9 stimuli. Treg can be substituted by TGFbeta1, which, together with the proinflammatory cytokine IL-6, sup...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2006.01.001

    authors： Veldhoen M,Hocking RJ,Atkins CJ,Locksley RM,Stockinger B

    更新日期：2006-02-01 00:00:00

  • Notch 1 signaling regulates peripheral T cell activation.

    abstract：:Notch signaling has been identified as an important regulator of leukocyte differentiation and thymic maturation. Less is known about the role of Notch signaling in regulating mature T cells. We examined the role of Notch 1 in regulating peripheral T cell activity in vitro and in vivo. Coligation of Notch 1 together w...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/s1074-7613(04)00081-0

    authors： Eagar TN,Tang Q,Wolfe M,He Y,Pear WS,Bluestone JA

    更新日期：2004-04-01 00:00:00

  • Gammadelta T cells and the lymphoid stress-surveillance response.

    abstract：:The investigation of gammadelta T cells has identified a rapid lymphoid stress-surveillance response to microbial and nonmicrobial tissue perturbation. In addition to providing local protection, this response provides an immediate source of cytokines, chemokines, and other functions that can substantially affect downs...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2009.08.006

    authors： Hayday AC

    更新日期：2009-08-21 00:00:00

  • The binding site for TRAF2 and TRAF3 but not for TRAF6 is essential for CD40-mediated immunoglobulin class switching.

    abstract：:To define the role of TRAF proteins in CD40-dependent isotype switching in B cells, we introduced wild-type (WT) and mutant CD40 transgenes that lacked the binding motifs for TRAF6 (CD40deltaTRAF6), TRAF2 and TRAF3 (CD40deltaTRAF2/3), or both (CD40deltaTRAFs) into B cells of CD40(-/-) mice. The in vivo isotype switch ...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/s1074-7613(02)00394-1

    authors： Jabara H,Laouini D,Tsitsikov E,Mizoguchi E,Bhan A,Castigli E,Dedeoglu F,Pivniouk V,Brodeur S,Geha R

    更新日期：2002-09-01 00:00:00

  • Pancreatic lymph node-derived CD4(+)CD25(+) Treg cells: highly potent regulators of diabetes that require TRANCE-RANK signals.

    abstract：:Inflammation can activate self-reactive CD8(+) T cells and induce autoimmunity. Here we show in a CD8(+) T cell-mediated model of type 1 diabetes that CD4(+)CD25(+) Treg cells prevent beta cell destruction following localized inflammation in the islets of Langerhans. These Treg cells accumulate preferentially in the p...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/s1074-7613(02)00279-0

    authors： Green EA,Choi Y,Flavell RA

    更新日期：2002-02-01 00:00:00

  • Caspase-8: clipping off RIG-I signaling.

    abstract：:Activation of the RIG-I signaling molecule is essential for antiviral immunity but mechanisms downmodulating the response are ill defined. In this issue of Immunity, Rajput et al. (2011) describe caspase-8-mediated RIP1 cleavage as a key step for restricting RIG-I signaling. ...

    journal_title：Immunity

    pub_type： 评论,杂志文章

    doi：10.1016/j.immuni.2011.03.011

    authors： Roth S,Ruland J

    更新日期：2011-03-25 00:00:00

  • Sweet NETs, Bitter Wounds.

    abstract：:What causes slow wound healing rates in diabetes is poorly understood. Wong et al. (2015) report that an increase in the deployment of neutrophil extracellular traps associated with hyperglycemia slows down wound healing. ...

    journal_title：Immunity

    pub_type： 评论,杂志文章

    doi：10.1016/j.immuni.2015.08.002

    authors： Papayannopoulos V

    更新日期：2015-08-18 00:00:00

  • Foxp3 and natural regulatory T cells: key to a cell lineage?

    abstract：:The recent characterization of a mutant strain of mice generated five decades ago in a program to study ionizing radiation in mammals (and, ironically, derived from a nonmutagenized control animal) is helping to dissect a now resurgent area of immunology. Despite a vast literature during the 1970s, the study of suppre...

    journal_title：Immunity

    pub_type： 杂志文章,评审

    doi：10.1016/s1074-7613(03)00207-3

    authors： Ramsdell F

    更新日期：2003-08-01 00:00:00

  • Memory B cells from human tonsils colonize mucosal epithelium and directly present antigen to T cells by rapid up-regulation of B7-1 and B7-2.

    abstract：:Human memory B cells that carry mutated IgV region genes were isolated from tonsils by negative selection of IgD+ naive B cells and CD38+ germinal center B cells and plasma cells. They were mainly found within the intraepithelial areas, but not in the B cell follicles of human tonsils. Memory B cells but not naive B c...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/1074-7613(95)90048-9

    authors： Liu YJ,Barthélémy C,de Bouteiller O,Arpin C,Durand I,Banchereau J

    更新日期：1995-03-01 00:00:00

  • The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans.

    abstract：:B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet+ and T-bet- memory B cells (MBCs) in the context of the influenza-specific immune response. In mi...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/j.immuni.2020.03.020

    authors： Johnson JL,Rosenthal RL,Knox JJ,Myles A,Naradikian MS,Madej J,Kostiv M,Rosenfeld AM,Meng W,Christensen SR,Hensley SE,Yewdell J,Canaday DH,Zhu J,McDermott AB,Dori Y,Itkin M,Wherry EJ,Pardi N,Weissman D,Naji A,Pra

    更新日期：2020-05-19 00:00:00

  • Delineating the genetic basis of systemic lupus erythematosus.

    abstract：:Genetic predisposition plays a crucial role in susceptibility to systemic lupus erythematosus (SLE) in both human patients and animal models. Recent progress in experimental systems and human linkage analysis is providing key insights into the genetic basis for susceptibility and elucidating the manner in which geneti...

    journal_title：Immunity

    pub_type： 杂志文章,评审

    doi：10.1016/s1074-7613(01)00201-1

    authors： Wakeland EK,Liu K,Graham RR,Behrens TW

    更新日期：2001-09-01 00:00:00

  • Recognition of pneumococcal peptidoglycan: an expanded, pivotal role for LPS binding protein.

    abstract：:Lipopolysaccharide binding protein (LBP) has a well-established role in LPS-induced immune responses. Here, we report that LBP also plays an essential role in the innate immune response to Gram-positive pneumococci, specifically to their major inflammatory component, pneumococcal cell wall (PCW). LBP was present in th...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/s1074-7613(03)00205-x

    authors： Weber JR,Freyer D,Alexander C,Schröder NW,Reiss A,Küster C,Pfeil D,Tuomanen EI,Schumann RR

    更新日期：2003-08-01 00:00:00

  • Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation.

    abstract：:We report essential roles of zinc finger transcription factor Gfi-1 in myeloid development. Gene-targeted Gfi-1(-/-) mice lack normal neutrophils and are highly susceptible to abscess formation by gram-positive bacteria. Arrested, morphologically atypical, Gr1(+)Mac1(+) myeloid cells expand with age in the bone marrow...

    journal_title：Immunity

    pub_type： 杂志文章

    doi：10.1016/s1074-7613(02)00501-0

    authors： Hock H,Hamblen MJ,Rooke HM,Traver D,Bronson RT,Cameron S,Orkin SH

    更新日期：2003-01-01 00:00:00