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

Abstract:

:Interleukin-6 (IL-6) levels are known to be increased in patients with rheumatoid arthritis (RA). Tocilizumab, a monoclonal antibody to the IL-6 receptor (IL-6R), reduces disease activity in RA, although its mechanisms of action remain unclear. Since IL-6 regulates cytokine production by CD4 T cells during activation, we investigated whether treatment with tocilizumab altered the phenotype and cytokine production by CD4 T cells in patients with rheumatoid arthritis. We show here that tocilizumab treatment does not change the production of cytokines by naïve CD4 T cells. However, tocilizumab treatment causes a selective decrease of IL-21 production by memory/activated CD4 T cells. Since IL-21 is known to promote plasma cell differentiation, we examined the effect of tocilizumab on the production of autoantibodies. We show that there is a decrease in the levels of IgG4 anti-CCP antibodies, but there is no effect on IgG1 anti-CCP antibodies. In addition, we show that IL-21 is a powerful inducer of IgG4 production by B cells. Thus, IL-6 contributes to the presence of IgG4-specific anti-CCP autoantibodies in RA patients, likely through its effect on IL-21 production by CD4 T cells, and IL-6R blockade down-regulates this pathway.

journal_name

Int J Biol Sci

authors

Carbone G,Wilson A,Diehl SA,Bunn J,Cooper SM,Rincon M

doi

10.7150/ijbs.5996

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

279-88

issue

3

issn

1449-2288

pii

ijbsv09p0279

journal_volume

9

pub_type

杂志文章
  • Vasa identifies germ cells and critical stages of oogenesis in the Asian seabass.

    abstract::Germ cells produce sperm and eggs for reproduction and fertility. The Asian seabass (Lates calcarifer), a protandrous marine fish, undergoes male-female sex reversal and thus offers an excellent model to study the role of germ cells in sex differentiation and sex reversal. Here we report the cloning and expression of ...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.6797

    authors: Xu H,Lim M,Dwarakanath M,Hong Y

    更新日期:2014-02-06 00:00:00

  • SIRT3 Activation by Dihydromyricetin Suppresses Chondrocytes Degeneration via Maintaining Mitochondrial Homeostasis.

    abstract::Mitochondrial dysfunction is an important contributor to the development of osteoarthritis (OA). Sirtuin 3 (SIRT3) regulates diverse mitochondrial proteins to maintain mitochondrial homeostasis, and dihydromyricetin (DHM) is reported as a potential SIRT3 activator. This study aims to explore the relevance of SIRT3 and...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.27746

    authors: Wang J,Wang K,Huang C,Lin D,Zhou Y,Wu Y,Tian N,Fan P,Pan X,Xu D,Hu J,Zhou Y,Wang X,Zhang X

    更新日期:2018-10-20 00:00:00

  • Genetic Variant in Flavin-Containing Monooxygenase 3 Alters Lipid Metabolism in Laying Hens in a Diet-Specific Manner.

    abstract::Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.16472

    authors: Wang J,Long C,Zhang H,Zhang Y,Wang H,Yue H,Wang X,Wu S,Qi G

    更新日期:2016-10-25 00:00:00

  • Melatonin Stimulates STAR Expression and Progesterone Production via Activation of the PI3K/AKT Pathway in Bovine Theca Cells.

    abstract::Melatonin is present in mammalian follicular fluid and plays an important role in regulating steroidogenesis in follicular cells. In this study, we report the effect of melatonin on steroidogenesis in the theca interna (TI) in small bovine follicles and theca cells (TCs) cultured in vitro. Treatment with melatonin sig...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.27912

    authors: Wang X,Meng K,He Y,Wang H,Zhang Y,Quan F

    更新日期:2019-01-01 00:00:00

  • BMP13 prevents the effects of annular injury in an ovine model.

    abstract::Chronic back pain is a global health problem affecting millions of people worldwide and carries significant economic and social morbidities. Intervertebral disc damage and degeneration is a major cause of back pain, characterised by histological and biochemical changes that have been well documented in animal models. ...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.5.388

    authors: Wei A,Williams LA,Bhargav D,Shen B,Kishen T,Duffy N,Diwan AD

    更新日期:2009-06-03 00:00:00

  • Identifying differentially expressed genes from cross-site integrated data based on relative expression orderings.

    abstract::It is a basic task in high-throughput gene expression profiling studies to identify differentially expressed genes (DEGs) between two phenotypes. But the weakly differential expression signals between two phenotypes are hardly detectable with limited sample sizes. To solve this problem, many researchers tried to combi...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.24548

    authors: Cai H,Li X,Li J,Liang Q,Zheng W,Guan Q,Guo Z,Wang X

    更新日期:2018-05-22 00:00:00

  • Different Modulatory Mechanisms of Renal FXYD12 for Na(+)-K(+)-ATPase between Two Closely Related Medakas upon Salinity Challenge.

    abstract::Upon salinity challenge, the Na(+)-K(+)-ATPase (NKA) of fish kidney plays a crucial role in maintaining ion and water balance. Moreover, the FXYD protein family was found to be a regulator of NKA. Our preliminary results revealed that fxyd12 was highly expressed in the kidneys of the two closely related euryhaline med...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.15066

    authors: Yang WK,Kang CK,Hsu AD,Lin CH,Lee TH

    更新日期:2016-04-28 00:00:00

  • SASH1 promotes melanin synthesis and migration via suppression of TGF-β1 secretion in melanocytes resulting in pathologic hyperpigmentation.

    abstract::Dyschromatosis universalis hereditaria (DUH) is an autosomal dominant pigmentary genodermatosis characterized by the presence of patches of hyperpigmentation and hypopigmented macules distributed over the body, with most cases reported in Asia. DUH is a heterogeneous disease and a small portion of patients carry the A...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.38415

    authors: Cui H,Guo S,He H,Guo H,Zhang Y,Wang B

    更新日期:2020-02-10 00:00:00

  • A comprehensive review of web-based resources of non-coding RNAs for plant science research.

    abstract::Non-coding RNAs (ncRNAs) are transcribed from genome but not translated into proteins. Many ncRNAs are key regulators of plants growth and development, metabolism and stress tolerance. In order to make the web-based ncRNA resources for plant science research be more easily accessible and understandable, we made a comp...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章,评审

    doi:10.7150/ijbs.24593

    authors: Liao P,Li S,Cui X,Zheng Y

    更新日期:2018-05-22 00:00:00

  • Dl-3-n-butylphthalide prevents the disruption of blood-spinal cord barrier via inhibiting endoplasmic reticulum stress following spinal cord injury.

    abstract::After spinal cord injury (SCI), the destruction of blood-spinal cord barrier (BSCB) is shown to accelerate gathering of noxious blood-derived components in the nervous system, leading to secondary neurodegenerative damages. SCI activates endoplasmic reticulum stress (ER stress), which is considered to evoke secondary ...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.21107

    authors: Zheng B,Zhou Y,Zhang H,Yang G,Hong Z,Han D,Wang Q,He Z,Liu Y,Wu F,Zhang X,Tong S,Xu H,Xiao J

    更新日期:2017-11-27 00:00:00

  • ACE2 Correlated With Immune Infiltration Serves As A Novel Prognostic Biomarker In Clear Cell Renal Cell Carcinoma: Implication For COVID-19.

    abstract::The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global infection, and is seriously threatening human life, especially cancer patients. Thus, we sought to determine the clinical roles of ACE2 (the cell entry receptor of SARS-CoV-2) in ccRCC (clear cell renal cell carcinoma). TCGA, ...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.51969

    authors: Yang W,Li L,Zhang K,Ma K,Xie H,Gong Y,Zhou J,Gong K

    更新日期:2021-01-01 00:00:00

  • Influence of carbon monoxide on growth and apoptosis of human umbilical artery smooth muscle cells and vein endothelial cells.

    abstract::Carbon monoxide (CO) is a vasoactive molecule that is generated by vascular cells as a byproduct of heme catabolism and it plays an important physiological role in circulation system. In order to investigate whether exogenous CO can mediate the growth and proliferation of vascular cells, in this study, we used 250 par...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.4664

    authors: Li Y,Wang H,Yang B,Yang J,Ruan X,Yang Y,Wakeland EK,Li Q,Fang X

    更新日期:2012-01-01 00:00:00

  • The gain of function of p53 mutant p53S in promoting tumorigenesis by cross-talking with H-RasV12.

    abstract::The loss of wild type p53 tumor suppressive function and oncogenic gain-of-function of p53 mutants have been showing important implications in tumorigenesis. The p53(N236S) (p53(N239S) in human, p53S) mutation has been shown to lose wild type p53 function by yeast assay. However, its gain of function is still not clea...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.4176

    authors: Jia S,Zhao L,Tang W,Luo Y

    更新日期:2012-01-01 00:00:00

  • MiR-696 Regulates C2C12 Cell Proliferation and Differentiation by Targeting CNTFRα.

    abstract::Micro-696 (miR-696) has been previously known as an exercise related miRNA, which has a profound role in fatty acid oxidation and mitochondrial biogenesis of skeletal muscle. However, its role in skeletal myoblast proliferation and differentiation is still unclear. In this study, we found that miR-696 expressed highly...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.17508

    authors: Wang H,Shi L,Liang T,Wang B,Wu W,Su G,Wei J,Li P,Huang R

    更新日期:2017-03-11 00:00:00

  • Enhanced cytotoxicity for colon 26 cells using doxorubicin-loaded sorbitan monooleate (Span 80) vesicles.

    abstract::Span 80 (sorbitan monooleate) vesicles behaved differently from conventional phospholipid vesicles (liposomes) because the former had a more fluid interface. After doxorubicin hydrochloride (DOX) was encapsulated into the Span 80 vesicle (loading efficiency: 63 %), DOX-loaded Span 80 vesicles (DVs) were thereafter add...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.5453

    authors: Hayashi K,Tatsui T,Shimanouchi T,Umakoshi H

    更新日期:2013-01-01 00:00:00

  • SMARCAD1 Promotes Pancreatic Cancer Cell Growth and Metastasis through Wnt/β-catenin-Mediated EMT.

    abstract::Pancreatic cancer (PC) is one of the most lethal diseases, characterized by early metastasis and high mortality. Subunits of the SWI/SNF complex have been identified in many studies as the regulators of tumor progression, but the role of SMARCAD1, one member of the SWI/SNF family, in pancreatic cancer has not been elu...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.29562

    authors: Liu F,Xia Z,Zhang M,Ding J,Feng Y,Wu J,Dong Y,Gao W,Han Z,Liu Y,Yao Y,Li D

    更新日期:2019-01-01 00:00:00

  • Repression of FGF signaling is responsible for Dnmt3b inhibition and impaired de novo DNA methylation during early development of in vitro fertilized embryos.

    abstract::Well-orchestrated epigenetic modifications during early development are essential for embryonic survival and postnatal growth. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various short- or long-term ...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.51607

    authors: Fu W,Yue Y,Miao K,Xi G,Zhang C,Wang W,An L,Tian J

    更新日期:2020-10-03 00:00:00

  • Inhibition of Estrogen Signaling Reduces the Incidence of BRCA1-associated Mammary Tumor Formation.

    abstract::BRCA1-deficient breast cancer is a very well-known hereditary cancer. However, except for resection of normal mammary glands and ovaries, there is no acceptable measure for proactively preventing tumor development. Importantly, inherited BRCA1 mutations are closely associated with tumors in hormone-responsive tissues....

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.28142

    authors: Baek HJ,Kim SE,Choi EK,Kim JK,Shin DH,Park EJ,Kim TH,Kim JY,Kim KG,Deng CX,Kim SS

    更新日期:2018-10-03 00:00:00

  • Collagen XXIV (Col24α1) promotes osteoblastic differentiation and mineralization through TGF-β/Smads signaling pathway.

    abstract::Collagen XXIV (Col24α1) is a recently discovered fibrillar collagen. It is known that mouse Col24α1 is predominantly expressed in the forming skeleton of the mouse embryo, as well as in the trabecular bone and periosteum of the newborn mouse. However, the role and mechanism of Col24α1 in osteoblast differentiation and...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.5136

    authors: Wang W,Olson D,Liang G,Franceschi RT,Li C,Wang B,Wang SS,Yang S

    更新日期:2012-01-01 00:00:00

  • Medaka tert produces multiple variants with differential expression during differentiation in vitro and in vivo.

    abstract::Embryonic stem (ES) cells have immortality for self-renewal and pluripotency. Differentiated human cells undergo replicative senescence. In human, the telomerase reverse transcriptase (Tert), namely the catalytic subunit of telomerase, exhibits differential expression to regulate telomerase activity governing cellular...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.7.426

    authors: Rao F,Wang T,Li M,Li Z,Hong N,Zhao H,Yan Y,Lu W,Chen T,Wang W,Lim M,Yuan Y,Liu L,Zeng L,Wei Q,Guan G,Li C,Hong Y

    更新日期:2011-04-15 00:00:00

  • Transarterial Chemoembolization: A Favorable Postoperative Management to Improve Prognosis of Hepatitis B Virus-associated Intrahepatic Cholangiocarcinoma after Surgical Resection.

    abstract::Background: There is no information regarding transarterial chemoembolization (TACE) as a postoperative management after hepatic resection for patients with hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC). Methods: Forty-two patients with pathological confirmation of HBV-associated ICC were en...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.21149

    authors: Jeong S,Zheng B,Wang J,Chi J,Tong Y,Xia L,Xu N,Zhang J,Kong X,Gu J,Xia Q

    更新日期:2017-09-21 00:00:00

  • Current Status of Therapeutic Approaches against Peripheral Nerve Injuries: A Detailed Story from Injury to Recovery.

    abstract::Peripheral nerve injury is a complex condition with a variety of signs and symptoms such as numbness, tingling, jabbing, throbbing, burning or sharp pain. Peripheral nerves are fragile in nature and can easily get damaged due to acute compression or trauma which may lead to the sensory and motor functions deficits and...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章,评审

    doi:10.7150/ijbs.35653

    authors: Hussain G,Wang J,Rasul A,Anwar H,Qasim M,Zafar S,Aziz N,Razzaq A,Hussain R,de Aguilar JG,Sun T

    更新日期:2020-01-01 00:00:00

  • Why would plant species become extinct locally if growing conditions improve?

    abstract::Two assumptions underlie current models of the geographical ranges of perennial plant species: 1. current ranges are in equilibrium with the prevailing climate, and 2. changes are attributable to changes in macroclimatic factors, including tolerance of winter cold, the duration of the growing season, and water stress ...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章,评审

    doi:10.7150/ijbs.4866

    authors: Kramer K,Bijlsma RJ,Hickler T,Thuiller W

    更新日期:2012-01-01 00:00:00

  • Enhanced antitumor efficacy of gemcitabine by evodiamine on pancreatic cancer via regulating PI3K/Akt pathway.

    abstract::Evodiamine has therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and evodiamine enhanced antitumor efficacy in pancreatic cancer. In vitro application of the combination therapy triggered significantly higher frequency of pancreatic cancer cells ...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.8.1

    authors: Wei WT,Chen H,Wang ZH,Ni ZL,Liu HB,Tong HF,Guo HC,Liu DL,Lin SZ

    更新日期:2012-01-01 00:00:00

  • Immune-related microRNAs are abundant in breast milk exosomes.

    abstract::Breast milk is a complex liquid rich in immunological components that affect the development of the infant's immune system. Exosomes are membranous vesicles of endocytic origin that are found in various body fluids and that can mediate intercellular communication. MicroRNAs (miRNAs), a well-defined group of non-coding...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.8.118

    authors: Zhou Q,Li M,Wang X,Li Q,Wang T,Zhu Q,Zhou X,Wang X,Gao X,Li X

    更新日期:2012-01-01 00:00:00

  • Icariin Inhibits Endoplasmic Reticulum Stress-induced Neuronal Apoptosis after Spinal Cord Injury through Modulating the PI3K/AKT Signaling Pathway.

    abstract::Endoplasmic reticulum (ER) stress-induced neuronal apoptosis is a crucial pathological process of spinal cord injury (SCI). In our previous study, icariin (ICA) showed neuroprotective effects in SCI. However, the relationships between ER stress and ICA in SCI are unclear yet. Therefore, whether ICA could ameliorate SC...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.30348

    authors: Li H,Zhang X,Qi X,Zhu X,Cheng L

    更新日期:2019-01-01 00:00:00

  • Potential Mechanisms of Action of Curcumin for Cancer Prevention: Focus on Cellular Signaling Pathways and miRNAs.

    abstract::Despite significant progressions in treatment modalities over the last decade, either cancer incidence or mortality is continuously on the rise throughout the world. Current anticancer agents display limited efficacy, accompanied by severe side effects. In order to improve therapeutic outcomes in patients with cancer,...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章,评审

    doi:10.7150/ijbs.33710

    authors: Wang M,Jiang S,Zhou L,Yu F,Ding H,Li P,Zhou M,Wang K

    更新日期:2019-05-07 00:00:00

  • A novel brain neurovascular unit model with neurons, astrocytes and microvascular endothelial cells of rat.

    abstract::A novel triple cell neurovascular unit (NVU) model co-culturing with neurons, brain microvascular endothelial cells (BMECs) and astrocytes was established in this study for investigating the cerebral diseases and screening the candidates of therapeutic drug. We have first performed the cell identification and morpholo...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.5115

    authors: Xue Q,Liu Y,Qi H,Ma Q,Xu L,Chen W,Chen G,Xu X

    更新日期:2013-01-01 00:00:00

  • Mammalian sirtuins and energy metabolism.

    abstract::Sirtuins are highly conserved NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies. The seven mammalian sirtuins, SIRT1 to SIRT7, have emerged as key metabolic sensors that directly link environmental signals t...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章,评审

    doi:10.7150/ijbs.7.575

    authors: Li X,Kazgan N

    更新日期:2011-01-01 00:00:00

  • Genome-wide association analysis of meat quality traits in a porcine Large White × Minzhu intercross population.

    abstract::Pork quality is an economically important trait and one of the main selection criteria for breeding in the swine industry. In this genome-wide association study (GWAS), 455 pigs from a porcine Large White × Minzhu intercross population were genotyped using the Illumina PorcineSNP60K Beadchip, and phenotyped for intram...

    journal_title:International journal of biological sciences

    pub_type: 杂志文章

    doi:10.7150/ijbs.3614

    authors: Luo W,Cheng D,Chen S,Wang L,Li Y,Ma X,Song X,Liu X,Li W,Liang J,Yan H,Zhao K,Wang C,Wang L,Zhang L

    更新日期:2012-01-01 00:00:00