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

Abstract:

:Foxp3(+) regulatory T (T(reg)) cells suppress different types of immune responses to help maintain homeostasis in the body. How T(reg) cells regulate humoral immunity, including germinal center reactions, is unclear. Here we identify a subset of T(reg) cells expressing CXCR5 and Bcl-6 that localize to the germinal centers in mice and humans. The expression of CXCR5 on T(reg) cells depends on Bcl-6. These CXCR5(+)Bcl-6(+) T(reg) cells are absent in the thymus but can be generated de novo from CXCR5(-)Foxp3(+) natural T(reg) precursors. A lack of CXCR5(+) T(reg) cells leads to greater germinal center reactions including germinal center B cells, affinity maturation of antibodies and the differentiation of plasma cells. These results unveil a Bcl-6-CXCR5 axis in T(reg) cells that drives the development of follicular regulatory T (T(FR)) cells that function to inhibit the germinal center reactions.

journal_name

Nat Med

journal_title

Nature medicine

authors

Chung Y,Tanaka S,Chu F,Nurieva RI,Martinez GJ,Rawal S,Wang YH,Lim H,Reynolds JM,Zhou XH,Fan HM,Liu ZM,Neelapu SS,Dong C

doi

10.1038/nm.2426

subject

Has Abstract

pub_date

2011-07-24 00:00:00

pages

983-8

issue

8

eissn

1078-8956

issn

1546-170X

pii

nm.2426

journal_volume

17

pub_type

杂志文章
  • Microbiota depletion promotes browning of white adipose tissue and reduces obesity.

    abstract::Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the ing...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3994

    authors: Suárez-Zamorano N,Fabbiano S,Chevalier C,Stojanović O,Colin DJ,Stevanović A,Veyrat-Durebex C,Tarallo V,Rigo D,Germain S,Ilievska M,Montet X,Seimbille Y,Hapfelmeier S,Trajkovski M

    更新日期:2015-12-01 00:00:00

  • Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms using a deep neural network.

    abstract::Computerized electrocardiogram (ECG) interpretation plays a critical role in the clinical ECG workflow1. Widely available digital ECG data and the algorithmic paradigm of deep learning2 present an opportunity to substantially improve the accuracy and scalability of automated ECG analysis. However, a comprehensive eval...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0268-3

    authors: Hannun AY,Rajpurkar P,Haghpanahi M,Tison GH,Bourn C,Turakhia MP,Ng AY

    更新日期:2019-01-01 00:00:00

  • Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis.

    abstract::Understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss, such as osteoporosis. Here we report that the C-C chemokine receptor-2 (CCR2) is crucially involved in balancing bone mass. CCR2-knockout mice have high bone mass owing to a decrease in n...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.1945

    authors: Binder NB,Niederreiter B,Hoffmann O,Stange R,Pap T,Stulnig TM,Mack M,Erben RG,Smolen JS,Redlich K

    更新日期:2009-04-01 00:00:00

  • Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis.

    abstract::Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of lymphatic vessels (...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/84643

    authors: Skobe M,Hawighorst T,Jackson DG,Prevo R,Janes L,Velasco P,Riccardi L,Alitalo K,Claffey K,Detmar M

    更新日期:2001-02-01 00:00:00

  • Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition.

    abstract::The role of KRAS, when activated through canonical mutations, has been well established in cancer1. Here we explore a secondary means of KRAS activation in cancer: focal high-level amplification of the KRAS gene in the absence of coding mutations. These amplifications occur most commonly in esophageal, gastric and ova...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0022-x

    authors: Wong GS,Zhou J,Liu JB,Wu Z,Xu X,Li T,Xu D,Schumacher SE,Puschhof J,McFarland J,Zou C,Dulak A,Henderson L,Xu P,O'Day E,Rendak R,Liao WL,Cecchi F,Hembrough T,Schwartz S,Szeto C,Rustgi AK,Wong KK,Diehl JA,Jen

    更新日期:2018-07-01 00:00:00

  • Autism risk in offspring can be assessed through quantification of male sperm mosaicism.

    abstract::De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessin...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-019-0711-0

    authors: Breuss MW,Antaki D,George RD,Kleiber M,James KN,Ball LL,Hong O,Mitra I,Yang X,Wirth SA,Gu J,Garcia CAB,Gujral M,Brandler WM,Musaev D,Nguyen A,McEvoy-Venneri J,Knox R,Sticca E,Botello MCC,Uribe Fenner J,Pérez MC

    更新日期:2020-01-01 00:00:00

  • Pharmacological inhibition of EGFR signaling enhances G-CSF-induced hematopoietic stem cell mobilization.

    abstract::Mobilization of hematopoietic stem and progenitor cells (HSPCs) from bone marrow into peripheral blood by the cytokine granulocyte colony-stimulating factor (G-CSF) has become the preferred source of HSPCs for stem cell transplants. However, G-CSF fails to mobilize sufficient numbers of stem cells in up to 10% of dono...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2217

    authors: Ryan MA,Nattamai KJ,Xing E,Schleimer D,Daria D,Sengupta A,Köhler A,Liu W,Gunzer M,Jansen M,Ratner N,Le Cras TD,Waterstrat A,Van Zant G,Cancelas JA,Zheng Y,Geiger H

    更新日期:2010-10-01 00:00:00

  • Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice.

    abstract::Immune evasion is an emerging hallmark of cancer progression. However, functional studies to understand the role of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment are limited by the lack of available specific cell surface markers. We adapted a competitive peptide phage display platform to ident...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3560

    authors: Qin H,Lerman B,Sakamaki I,Wei G,Cha SC,Rao SS,Qian J,Hailemichael Y,Nurieva R,Dwyer KC,Roth J,Yi Q,Overwijk WW,Kwak LW

    更新日期:2014-06-01 00:00:00

  • Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer.

    abstract::Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a singl...

    journal_title:Nature medicine

    pub_type: 杂志文章,随机对照试验

    doi:10.1038/nm1310

    authors: Rapoport AP,Stadtmauer EA,Aqui N,Badros A,Cotte J,Chrisley L,Veloso E,Zheng Z,Westphal S,Mair R,Chi N,Ratterree B,Pochran MF,Natt S,Hinkle J,Sickles C,Sohal A,Ruehle K,Lynch C,Zhang L,Porter DL,Luger S,Guo C,

    更新日期:2005-11-01 00:00:00

  • Anomalously warm temperatures are associated with increased injury deaths.

    abstract::Temperatures that deviate from the long-term local norm affect human health, and are projected to become more frequent as the global climate changes1. There are limited data on how such anomalies affect deaths from injuries. In the present study, we used data on mortality and temperature over 38 years (1980-2017) in t...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-019-0721-y

    authors: Parks RM,Bennett JE,Tamura-Wicks H,Kontis V,Toumi R,Danaei G,Ezzati M

    更新日期:2020-01-01 00:00:00

  • Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery.

    abstract::Skin is an attractive target for delivery of genetic therapies and vaccines. However, new approaches are needed to access this tissue more effectively. Here, we describe a new delivery technology based on arrays of structurally precise, micron-scale silicon projections, which we term microenhancer arrays (MEAs). In a ...

    journal_title:Nature medicine

    pub_type: 临床试验,杂志文章

    doi:10.1038/nm0402-415

    authors: Mikszta JA,Alarcon JB,Brittingham JM,Sutter DE,Pettis RJ,Harvey NG

    更新日期:2002-04-01 00:00:00

  • Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects.

    abstract::Preservation of the chemical architecture of a cell or of an organism under changing and perhaps stressful conditions is termed homeostasis. An integral feature of homeostasis is the rapid expression of genes whose products are specifically dedicated to protect cellular functions against stress. One of the best known ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1097-1150

    authors: Vígh L,Literáti PN,Horváth I,Török Z,Balogh G,Glatz A,Kovács E,Boros I,Ferdinándy P,Farkas B,Jaszlits L,Jednákovits A,Korányi L,Maresca B

    更新日期:1997-10-01 00:00:00

  • Immunity or tolerance: opposite outcomes of microchimerism from skin grafts.

    abstract::Solid organ transplants contain small numbers of leukocytes that can migrate into the host and establish long-lasting microchimerism. Although such microchimerism is often associated with graft acceptance and tolerance, it has been difficult to demonstrate a true causal link. Using skin from mutant mice deficient for ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/83393

    authors: Anderson CC,Matzinger P

    更新日期:2001-01-01 00:00:00

  • Interleukin-6-deficient mice develop mature-onset obesity.

    abstract::The immune-modulating cytokine interleukin-6 (IL-6) is expressed both in adipose tissue and centrally in hypothalamic nuclei that regulate body composition. We investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding IL-6 (Il6-/- mice) and found that they developed mature-onset obe...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0102-75

    authors: Wallenius V,Wallenius K,Ahrén B,Rudling M,Carlsten H,Dickson SL,Ohlsson C,Jansson JO

    更新日期:2002-01-01 00:00:00

  • In vivo site-directed mutagenesis of the factor IX gene by chimeric RNA/DNA oligonucleotides.

    abstract::A chimeric RNA/DNA oligonucleotide was constructed to induce a sequence mutation in the rat factor IX gene, resulting in prolonged coagulation. Oligonucleotides were targeted to hepatocytes in cell culture or in vivo by intravenous injection. Nucleotide conversion was both site-specific and dose-dependent. The mutated...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0398-285

    authors: Kren BT,Bandyopadhyay P,Steer CJ

    更新日期:1998-03-01 00:00:00

  • Deacetylase inhibition promotes the generation and function of regulatory T cells.

    abstract::Histone/protein deacetylases (HDACs) regulate chromatin remodeling and gene expression as well as the functions of more than 50 transcription factors and nonhistone proteins. We found that administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the production and suppressive fun...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1652

    authors: Tao R,de Zoeten EF,Ozkaynak E,Chen C,Wang L,Porrett PM,Li B,Turka LA,Olson EN,Greene MI,Wells AD,Hancock WW

    更新日期:2007-11-01 00:00:00

  • Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria.

    abstract::The role of nitric oxide (NO) in the genesis of cerebral malaria is controversial. Most investigators propose that the unfortunate consequence of the high concentrations of NO produced to kill the parasite is the development of cerebral malaria. Here we have tested this high NO bioavailability hypothesis in the settin...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1499

    authors: Gramaglia I,Sobolewski P,Meays D,Contreras R,Nolan JP,Frangos JA,Intaglietta M,van der Heyde HC

    更新日期:2006-12-01 00:00:00

  • Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions.

    abstract::The molecular alterations that occur in cells before cancer is manifest are largely uncharted. Lung carcinoma in situ (CIS) lesions are the pre-invasive precursor to squamous cell carcinoma. Although microscopically identical, their future is in equipoise, with half progressing to invasive cancer and half regressing o...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0323-0

    authors: Teixeira VH,Pipinikas CP,Pennycuick A,Lee-Six H,Chandrasekharan D,Beane J,Morris TJ,Karpathakis A,Feber A,Breeze CE,Ntolios P,Hynds RE,Falzon M,Capitanio A,Carroll B,Durrenberger PF,Hardavella G,Brown JM,Lynch AG,Fa

    更新日期:2019-03-01 00:00:00

  • Epigenetic modulation of the renal β-adrenergic-WNK4 pathway in salt-sensitive hypertension.

    abstract::How high salt intake increases blood pressure is a key question in the study of hypertension. Salt intake induces increased renal sympathetic activity resulting in sodium retention. However, the mechanisms underlying the sympathetic control of renal sodium excretion remain unclear. In this study, we found that β(2)-ad...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2337

    authors: Mu S,Shimosawa T,Ogura S,Wang H,Uetake Y,Kawakami-Mori F,Marumo T,Yatomi Y,Geller DS,Tanaka H,Fujita T

    更新日期:2011-05-01 00:00:00

  • T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers.

    abstract::Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-020-0858-8

    authors: Arunachalam PS,Charles TP,Joag V,Bollimpelli VS,Scott MKD,Wimmers F,Burton SL,Labranche CC,Petitdemange C,Gangadhara S,Styles TM,Quarnstrom CF,Walter KA,Ketas TJ,Legere T,Jagadeesh Reddy PB,Kasturi SP,Tsai A,Yeung BZ

    更新日期:2020-06-01 00:00:00

  • Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays.

    abstract::Naturally occurring mutations in HIV-1-infected patients have important implications for therapy and the outcome of clinical studies. However, little is known about the prevalence of mutations that confer resistance to HIV-1 protease inhibitors in isolates derived from patients naive for such inhibitors. In the first ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0796-753

    authors: Kozal MJ,Shah N,Shen N,Yang R,Fucini R,Merigan TC,Richman DD,Morris D,Hubbell E,Chee M,Gingeras TR

    更新日期:1996-07-01 00:00:00

  • Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough.

    abstract::Cough accompanied by an increased sensitivity of the cough reflex is the most common symptom of inflammatory airway disease. This symptom is also frequently reported in patients receiving angiotensin-converting enzyme (ACE) inhibitors as therapy for heart failure or hypertension, although the underlying mechanism is u...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0796-814

    authors: Fox AJ,Lalloo UG,Belvisi MG,Bernareggi M,Chung KF,Barnes PJ

    更新日期:1996-07-01 00:00:00

  • HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy.

    abstract::Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in its hosts and is never eradicated. One major barrier to eradication is that the virus infects multiple cell types that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV pathogenesis; howev...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4319

    authors: Honeycutt JB,Thayer WO,Baker CE,Ribeiro RM,Lada SM,Cao Y,Cleary RA,Hudgens MG,Richman DD,Garcia JV

    更新日期:2017-05-01 00:00:00

  • v-ATPase V0 subunit d2-deficient mice exhibit impaired osteoclast fusion and increased bone formation.

    abstract::Matrix-producing osteoblasts and bone-resorbing osteoclasts maintain bone homeostasis. Osteoclasts are multinucleated, giant cells of hematopoietic origin formed by the fusion of mononuclear pre-osteoclasts derived from myeloid cells. Fusion-mediated giant cell formation is critical for osteoclast maturation; without ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1514

    authors: Lee SH,Rho J,Jeong D,Sul JY,Kim T,Kim N,Kang JS,Miyamoto T,Suda T,Lee SK,Pignolo RJ,Koczon-Jaremko B,Lorenzo J,Choi Y

    更新日期:2006-12-01 00:00:00

  • A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1.

    abstract::Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, for which there is no proven therapy. Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease. The disease begins in utero and is slowly progressive, but it is not known whether cystogenesi...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1675

    authors: Piontek K,Menezes LF,Garcia-Gonzalez MA,Huso DL,Germino GG

    更新日期:2007-12-01 00:00:00

  • Reversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome.

    abstract::Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthes...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1204

    authors: Scaffidi P,Misteli T

    更新日期:2005-04-01 00:00:00

  • A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors.

    abstract::Single-cell genomics is essential to chart tumor ecosystems. Although single-cell RNA-Seq (scRNA-Seq) profiles RNA from cells dissociated from fresh tumors, single-nucleus RNA-Seq (snRNA-Seq) is needed to profile frozen or hard-to-dissociate tumors. Each requires customization to different tissue and tumor types, posi...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-020-0844-1

    authors: Slyper M,Porter CBM,Ashenberg O,Waldman J,Drokhlyansky E,Wakiro I,Smillie C,Smith-Rosario G,Wu J,Dionne D,Vigneau S,Jané-Valbuena J,Tickle TL,Napolitano S,Su MJ,Patel AG,Karlstrom A,Gritsch S,Nomura M,Waghray A,Go

    更新日期:2020-05-01 00:00:00

  • Imaging 26S proteasome activity and inhibition in living mice.

    abstract::The ubiquitin-proteasome pathway is the central mediator of regulated proteolysis in cells, and defects in this pathway are associated with cancer and neurodegenerative diseases. To assess 26S proteasome function in living animals, we developed a ubiquitin-luciferase reporter for bioluminescence imaging. The reporter ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm894

    authors: Luker GD,Pica CM,Song J,Luker KE,Piwnica-Worms D

    更新日期:2003-07-01 00:00:00

  • Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor.

    abstract::The androgen receptor (AR) is involved in the development, growth and progression of prostate cancer (CaP). CaP often progresses from an androgen-dependent to an androgen-independent tumor, making androgen ablation therapy ineffective. However, the mechanisms for the development of androgen-independent CaP are unclear...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/76287

    authors: Zhao XY,Malloy PJ,Krishnan AV,Swami S,Navone NM,Peehl DM,Feldman D

    更新日期:2000-06-01 00:00:00

  • Adding to the checkpoint blockade armamentarium.

    abstract:: ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-019-0350-5

    authors: Hellmann MD,Snyder A

    更新日期:2019-02-01 00:00:00