Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells.


:Fever, an evolutionarily conserved physiological response to infection, is also commonly associated with many autoimmune diseases, but its role in T cell differentiation and autoimmunity remains largely unclear. T helper 17 (Th17) cells are critical in host defense and autoinflammatory diseases, with distinct phenotypes and pathogenicity. Here, we show that febrile temperature selectively regulated Th17 cell differentiation in vitro in enhancing interleukin-17 (IL-17), IL-17F, and IL-22 expression. Th17 cells generated under febrile temperature (38.5°C-39.5°C), compared with those under 37°C, showed enhanced pathogenic gene expression with increased pro-inflammatory activities in vivo. Mechanistically, febrile temperature promoted SUMOylation of SMAD4 transcription factor to facilitate its nuclear localization; SMAD4 deficiency selectively abrogated the effects of febrile temperature on Th17 cell differentiation both in vitro and ameliorated an autoimmune disease model. Our results thus demonstrate a critical role of fever in shaping adaptive immune responses with implications in autoimmune diseases.






Wang X,Ni L,Wan S,Zhao X,Ding X,Dejean A,Dong C




Has Abstract


2020-02-18 00:00:00
















  • Cytotoxic T cell-resistant variants are selected in a virus-induced demyelinating disease.

    abstract::C57BI/6 mice infected with mouse hepatitis virus, strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis. Infectious virus can be isolated only from symptomatic mice. In C57BI/6 mice, two CD8+ T cell epitopes within the MHV-JHM surface glycoprotein were previously identified. Here, we show that mutatio...


    pub_type: 杂志文章


    authors: Pewe L,Wu GF,Barnett EM,Castro RF,Perlman S

    更新日期:1996-09-01 00:00:00

  • Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia.

    abstract::The ETS gene Fli-1 is involved in the induction of erythroleukemia in mice by Friend murine leukemia virus and Ewings sarcoma in children. Mice with a targeted null mutation in the Fli-1 locus die at day 11.5 of embryogenesis with loss of vascular integrity leading to bleeding within the vascular plexus of the cerebra...


    pub_type: 杂志文章


    authors: Hart A,Melet F,Grossfeld P,Chien K,Jones C,Tunnacliffe A,Favier R,Bernstein A

    更新日期:2000-08-01 00:00:00

  • Is EBV persistence in vivo a model for B cell homeostasis?

    abstract::We have measured the absolute numbers of EBV-infected B cells in the peripheral blood of healthy persistently infected individuals. Single measurements on a panel of 15 healthy individuals demonstrate that the frequency varies over a wide range from 1-50 per 10(6) B cells. Repeat measurements over 1-3.5 years on sever...


    pub_type: 杂志文章


    authors: Khan G,Miyashita EM,Yang B,Babcock GJ,Thorley-Lawson DA

    更新日期:1996-08-01 00:00:00

  • The distal V(H) gene cluster of the Igh locus contains distinct regulatory elements with Pax5 transcription factor-dependent activity in pro-B cells.

    abstract::V(H)-DJ(H) recombination of the immunoglobulin heavy chain (Igh) locus is temporally and spatially controlled during early B cell development, and yet no regulatory elements other than the V(H) gene promoters have been identified throughout the entire V(H) gene cluster. Here, we discovered regulatory sequences that ar...


    pub_type: 杂志文章


    authors: Ebert A,McManus S,Tagoh H,Medvedovic J,Salvagiotto G,Novatchkova M,Tamir I,Sommer A,Jaritz M,Busslinger M

    更新日期:2011-02-25 00:00:00

  • Actin depletion initiates events leading to granule secretion at the immunological synapse.

    abstract::Cytotoxic T lymphocytes (CTLs) use polarized secretion to rapidly destroy virally infected and tumor cells. To understand the temporal relationships between key events leading to secretion, we used high-resolution 4D imaging. CTLs approached targets with actin-rich projections at the leading edge, creating an initiall...


    pub_type: 杂志文章


    authors: Ritter AT,Asano Y,Stinchcombe JC,Dieckmann NM,Chen BC,Gawden-Bone C,van Engelenburg S,Legant W,Gao L,Davidson MW,Betzig E,Lippincott-Schwartz J,Griffiths GM

    更新日期:2015-05-19 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...


    pub_type: 杂志文章


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

    更新日期:2001-03-01 00:00:00

  • Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer.

    abstract::Numerous regulatory programs have been identified that contribute to the restoration of homeostasis at the conclusion of immune responses and to safeguarding against the detrimental effects of chronic inflammation and autoimmune pathology. Malignant cells may usurp these pathways to create immunosuppressive networks t...


    pub_type: 杂志文章,评审


    authors: Rabinovich GA,Croci DO

    更新日期:2012-03-23 00:00:00

  • Development of Foxp3(+) regulatory t cells is driven by the c-Rel enhanceosome.

    abstract::Regulatory T (Treg) cells are essential for maintaining immune homeostasis. Although Foxp3 expression marks the commitment of progenitors to Treg cell lineage, how Treg cells are generated during lymphocyte development remains enigmatic. We report here that the c-Rel transcription factor controlled development of Treg...


    pub_type: 杂志文章


    authors: Ruan Q,Kameswaran V,Tone Y,Li L,Liou HC,Greene MI,Tone M,Chen YH

    更新日期:2009-12-18 00:00:00

  • The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells.

    abstract::Type 2 innate lymphoid cells (ILC2s) are part of a large family of ILCs that are important effectors in innate immunity, lymphoid organogenesis, and tissue remodeling. ILC2s mediate parasite expulsion but also contribute to airway inflammation, emphasizing the functional similarity between these cells and Th2 cells. C...


    pub_type: 杂志文章


    authors: Mjösberg J,Bernink J,Golebski K,Karrich JJ,Peters CP,Blom B,te Velde AA,Fokkens WJ,van Drunen CM,Spits H

    更新日期:2012-10-19 00:00:00

  • A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation.

    abstract::The epidermal growth factor receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis after injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functioned by releasing bioactive transforming growth facto...


    pub_type: 杂志文章


    authors: Minutti CM,Modak RV,Macdonald F,Li F,Smyth DJ,Dorward DA,Blair N,Husovsky C,Muir A,Giampazolias E,Dobie R,Maizels RM,Kendall TJ,Griggs DW,Kopf M,Henderson NC,Zaiss DM

    更新日期:2019-03-19 00:00:00

  • Aiolos regulates B cell activation and maturation to effector state.

    abstract::Aiolos encodes a zinc finger DNA-binding protein that is highly expressed in mature B cells and is homologous to Ikaros. In the periphery of mice homozygous for an Aiolos-null mutation, B cells exhibit an activated cell surface phenotype and undergo augmented antigen receptor (BCR)-mediated in vitro proliferative resp...


    pub_type: 杂志文章


    authors: Wang JH,Avitahl N,Cariappa A,Friedrich C,Ikeda T,Renold A,Andrikopoulos K,Liang L,Pillai S,Morgan BA,Georgopoulos K

    更新日期:1998-10-01 00:00:00

  • Developing lymph nodes collect CD4+CD3- LTbeta+ cells that can differentiate to APC, NK cells, and follicular cells but not T or B cells.

    abstract::For a brief period during fetal lymph node organogenesis in mice, lymph node postcapillary high endothelial venules surprisingly express the Peyer's patch addressin MAdCAM-1. This expression allows initial seeding of this incipient structure by two unusual lymphocyte populations selectively expressing the Peyer's patc...


    pub_type: 杂志文章


    authors: Mebius RE,Rennert P,Weissman IL

    更新日期:1997-10-01 00:00:00

  • Frequencies of multiple IgL chain gene rearrangements in single normal or kappaL chain-deficient B lineage cells.

    abstract::PCR analyses of the kappaL chain locus in single B-lineage cells of wild-type, Ckappa-, or JCkappa-deficient homozygous or heterozygous mice often detect multiple in- and out-of-frame rearrangements at the kappaL and lambdaL loci. They are most frequent in small pre-BII cells and equally so in wild-type and kappaL cha...


    pub_type: 杂志文章


    authors: Yamagami T,ten Boekel E,Andersson J,Rolink A,Melchers F

    更新日期:1999-09-01 00:00:00

  • IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells.

    abstract::An efficient Th1-driven adaptive immune response requires activation of the T cell receptor and secretion of the T cell stimulatory cytokine IL-12 by activated antigen-presenting cells. IL-12 triggers Th1 polarization of naive CD4(+) T cells and secretion of IFN-gamma. We describe a new heterodimeric cytokine termed I...


    pub_type: 杂志文章


    authors: Pflanz S,Timans JC,Cheung J,Rosales R,Kanzler H,Gilbert J,Hibbert L,Churakova T,Travis M,Vaisberg E,Blumenschein WM,Mattson JD,Wagner JL,To W,Zurawski S,McClanahan TK,Gorman DM,Bazan JF,de Waal Malefyt R,Rennick D,

    更新日期:2002-06-01 00:00:00

  • Caspases in Cell Death, Inflammation, and Disease.

    abstract::Caspases are an evolutionary conserved family of cysteine proteases that are centrally involved in cell death and inflammation responses. A wealth of foundational insight into the molecular mechanisms that control caspase activation has emerged in recent years. Important advancements include the identification of addi...


    pub_type: 杂志文章,评审


    authors: Van Opdenbosch N,Lamkanfi M

    更新日期:2019-06-18 00:00:00

  • MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion.

    abstract::Group 2 innate lymphoid cells (ILC2s) release interleukin-13 (IL-13) during protective immunity to helminth infection and detrimentally during allergy and asthma. Using two mouse models to deplete ILC2s in vivo, we demonstrate that T helper 2 (Th2) cell responses are impaired in the absence of ILC2s. We show that MHCI...


    pub_type: 杂志文章


    authors: Oliphant CJ,Hwang YY,Walker JA,Salimi M,Wong SH,Brewer JM,Englezakis A,Barlow JL,Hams E,Scanlon ST,Ogg GS,Fallon PG,McKenzie AN

    更新日期:2014-08-21 00:00:00

  • Critical role for NALP3/CIAS1/Cryopyrin in innate and adaptive immunity through its regulation of caspase-1.

    abstract::Mutations in the NALP3/CIAS1/cryopyrin gene are linked to three autoinflammatory disorders: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and chronic infantile neurologic cutaneous and articular syndrome. NALP3, with the adaptor molecule ASC, has been proposed to form a caspase-1-activating "inflamma...


    pub_type: 杂志文章


    authors: Sutterwala FS,Ogura Y,Szczepanik M,Lara-Tejero M,Lichtenberger GS,Grant EP,Bertin J,Coyle AJ,Galán JE,Askenase PW,Flavell RA

    更新日期:2006-03-01 00:00:00

  • CD28 superagonists: what makes the difference in humans?

    abstract::In 2006, a clinical trial with the CD28 superagonistic antibody TGN1412 in London turned into a catastrophe. Studies are beginning to unravel the difference between the human and preclinical animal response to the antibody. ...


    pub_type: 杂志文章


    authors: Schraven B,Kalinke U

    更新日期:2008-05-01 00:00:00

  • Nonconventional initiation complex assembly by STAT and NF-kappaB transcription factors regulates nitric oxide synthase expression.

    abstract::Transcriptional regulation of the Nos2 gene encoding inducible nitric oxide synthase (iNOS) requires type I interferon (IFN-I) signaling and additional signals emanating from pattern recognition receptors. Here we showed sequential and cooperative contributions of the transcription factors ISGF3 (a complex containing ...


    pub_type: 杂志文章


    authors: Farlik M,Reutterer B,Schindler C,Greten F,Vogl C,Müller M,Decker T

    更新日期:2010-07-23 00:00:00

  • The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator.

    abstract::The thymic medulla provides a microenvironment where medullary thymic epithelial cells (mTECs) express autoimmune regulator and diverse tissue-restricted genes, contributing to launching self-tolerance. Positive selection is essential for thymic medulla formation via a previously unknown mechanism. Here we show that t...


    pub_type: 杂志文章


    authors: Hikosaka Y,Nitta T,Ohigashi I,Yano K,Ishimaru N,Hayashi Y,Matsumoto M,Matsuo K,Penninger JM,Takayanagi H,Yokota Y,Yamada H,Yoshikai Y,Inoue J,Akiyama T,Takahama Y

    更新日期:2008-09-19 00:00:00

  • FAS Inactivation Releases Unconventional Germinal Center B Cells that Escape Antigen Control and Drive IgE and Autoantibody Production.

    abstract::The mechanistic links between genetic variation and autoantibody production in autoimmune disease remain obscure. Autoimmune lymphoproliferative syndrome (ALPS) is caused by inactivating mutations in FAS or FASL, with autoantibodies thought to arise through failure of FAS-mediated removal of self-reactive germinal cen...


    pub_type: 杂志文章


    authors: Butt D,Chan TD,Bourne K,Hermes JR,Nguyen A,Statham A,O'Reilly LA,Strasser A,Price S,Schofield P,Christ D,Basten A,Ma CS,Tangye SG,Phan TG,Rao VK,Brink R

    更新日期:2015-05-19 00:00:00

  • Multifaceted Effects of Antigen Valency on B Cell Response Composition and Differentiation In Vivo.

    abstract::How antigen valency affects B cells in vivo during immune responses is not well understood. Here, using HIV immunogens with defined valencies ranging from 1 to 60, we investigated the role of antigen valency during different phases of B cell responses in vivo. Highly multimerized immunogens preferentially rapidly acti...


    pub_type: 杂志文章


    authors: Kato Y,Abbott RK,Freeman BL,Haupt S,Groschel B,Silva M,Menis S,Irvine DJ,Schief WR,Crotty S

    更新日期:2020-09-15 00:00:00

  • Differential TCR signaling regulates apoptosis and immunopathology during antigen responses in vivo.

    abstract::Clonal selection theories postulate that lymphocyte fate is regulated by antigen receptor specificity. However, lymphocyte apoptosis is induced through nonantigen-specific receptors such as Fas (CD95/APO-1) or TNFR. We define a selective TCR that controls apoptosis by Fas or TNFR stimulation. Variant ligands can deliv...


    pub_type: 杂志文章


    authors: Combadière B,Reis e Sousa C,Trageser C,Zheng LX,Kim CR,Lenardo MJ

    更新日期:1998-09-01 00:00:00

  • The crystal structure of H-2Dd MHC class I complexed with the HIV-1-derived peptide P18-I10 at 2.4 A resolution: implications for T cell and NK cell recognition.

    abstract::The structure of H-2Dd complexed with the HIV-derived peptide P18-I10 (RGPGRAFVTI) has been determined by X-ray crystallography at 2.4 A resolution. This MHC class I molecule has an unusual binding motif with four anchor residues in the peptide (G2, P3, R/K/H5, and I/L/F9 or 10). The cleft architecture of H-2Dd includ...


    pub_type: 杂志文章


    authors: Achour A,Persson K,Harris RA,Sundbäck J,Sentman CL,Lindqvist Y,Schneider G,Kärre K

    更新日期:1998-08-01 00:00:00

  • Histone Deacetylase SIRT1 Negatively Regulates the Differentiation of Interleukin-9-Producing CD4(+) T Cells.

    abstract::Distinct metabolic programs support the differentiation of CD4(+) T cells into separate functional subsets. In this study, we investigated metabolic mechanisms underlying the differentiation of IL-9-producing CD4(+) T cells (Th9) in allergic airway inflammation and cancerous tumors. We found that histone deacetylase S...


    pub_type: 杂志文章


    authors: Wang Y,Bi Y,Chen X,Li C,Li Y,Zhang Z,Wang J,Lu Y,Yu Q,Su H,Yang H,Liu G

    更新日期:2016-06-21 00:00:00

  • Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes.

    abstract::For several days after antigenic stimulation, human cytolytic T lymphocyte (CTL) clones exhibit a decrease in their effector activity and in their binding to human leukocyte antigen (HLA)-peptide tetramers. We observed that, when in this state, CTLs lose the colocalization of the T cell receptor (TCR) and CD8. Effecto...


    pub_type: 杂志文章


    authors: Demotte N,Stroobant V,Courtoy PJ,Van Der Smissen P,Colau D,Luescher IF,Hivroz C,Nicaise J,Squifflet JL,Mourad M,Godelaine D,Boon T,van der Bruggen P

    更新日期:2008-03-01 00:00:00

  • Non-canonical NF-κB Antagonizes STING Sensor-Mediated DNA Sensing in Radiotherapy.

    abstract::The NF-κB pathway plays a crucial role in supporting tumor initiation, progression, and radioresistance of tumor cells. However, the role of the NF-κB pathway in radiation-induced anti-tumor host immunity remains unclear. Here we demonstrated that inhibiting the canonical NF-κB pathway dampened the therapeutic effect ...


    pub_type: 杂志文章


    authors: Hou Y,Liang H,Rao E,Zheng W,Huang X,Deng L,Zhang Y,Yu X,Xu M,Mauceri H,Arina A,Weichselbaum RR,Fu YX

    更新日期:2018-09-18 00:00:00

  • The Neuropeptide CGRP Induces Bipolar Syndrome in Group 2 Innate Lymphoid Cells.

    abstract::In this issue of Immunity, Nagashima et al., Wallrapp et al., and Xu et al. demonstrate that the neuropeptide calcitonin gene-related peptide (CGRP) fine tunes type 2 innate immune response via suppressing group 2 innate lymphoid cells (ILC2s). ...


    pub_type: 评论,杂志文章


    authors: Motomura Y,Kobayashi T,Moro K

    更新日期:2019-10-15 00:00:00

  • A RHIM with a View: FLYing with Functional Amyloids.

    abstract::Recognition of bacterial peptidoglycan by the Drosophila IMD pathway triggers NF-κB activation and an associated immune response. In this issue of Immunity, Kleino et al. (2017) show that proteins in the IMD pathway form functional amyloids via a cryptic motif resembling the RHIM motif found in mammalian RIPK proteins...


    pub_type: 评论,杂志文章


    authors: Shin S,Cherry S

    更新日期:2017-10-17 00:00:00

  • HIV-1-induced thymocyte depletion is associated with indirect cytopathogenicity and infection of progenitor cells in vivo.

    abstract::Direct and indirect cytopathic mechanisms have been proposed to account for the loss of CD4+ T cells after infection with human immunodeficiency virus type 1 (HIV-1). We report here that HIV-1 infection of the human thymus in vivo results in thymocyte depletion by at least two different mechanisms. Thymocytes within m...


    pub_type: 杂志文章


    authors: Su L,Kaneshima H,Bonyhadi M,Salimi S,Kraft D,Rabin L,McCune JM

    更新日期:1995-01-01 00:00:00