DOCSLIB.ORG

Targeting IL-10 Family Cytokines for the Treatment of Human Diseases

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Targeting IL-10 Family Cytokines for the Treatment of Human Diseases Downloaded from http://cshperspectives.cshlp.org/ on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Targeting IL-10 Family Cytokines for the Treatment of Human Diseases Xiaoting Wang,1 Kit Wong,2 Wenjun Ouyang,3 and Sascha Rutz4 1Department of Comparative Biology and Safety Sciences, Amgen, South San Francisco, California 94080 2Department of Biomarker Development, Genentech, South San Francisco, California 94080 3Department of Inflammation and Oncology, Amgen, South San Francisco, California 94080 4Department of Cancer Immunology, Genentech, South San Francisco, California 94080 Correspondence: [email protected]; [email protected] Members of the interleukin (IL)-10 family of cytokines play important roles in regulating immune responses during host defense but also in autoimmune disorders, inflammatory diseases, and cancer. Although IL-10 itself primarily acts on leukocytes and has potent immunosuppressive functions, other family members preferentially target nonimmune com- partments, such as tissue epithelial cells, where they elicit innate defense mechanisms to control viral, bacterial, and fungal infections, protect tissue integrity, and promote tissue repair and regeneration. As cytokines are prime drug targets, IL-10 family cytokines provide great opportunities for the treatment of autoimmune diseases, tissue damage, and cancer. Yet no therapy in this space has been approved to date. Here, we summarize the diverse biology of the IL-10 family as it relates to human disease and review past and current strategies and challenges to target IL-10 family cytokines for clinical use. nterleukin (IL)-10, a cytokine with pleiotropic kines (Fiorentino et al. 1989). It has since been Iimmunosuppressive functions, is also the found that IL-10 is expressed by a wide variety of founding member of the IL-10 family of cyto- cell types of both the innate and the adaptive kines (Fig. 1). In addition to IL-10 itself, this arms of the immune system, including macro- group of cytokines encompasses IL-19, IL-20, phages, monocytes, dendritic cells (DCs), mast IL-22, IL-24, and IL-26, which are collectively cells, eosinophils, neutrophils, natural killer referred to as the IL-20 subfamily, as well as the (NK) cells, CD4+ and CD8+ T cells, and B cells more distantly related members IL-28A, IL-28B, (Moore et al. 2001; Ouyang et al. 2011). IL-20 and IL-29, also known as the interferon (IFN)-λ subfamily cytokines are also produced mainly family or type III IFNs (Pestka et al. 2004; Ou- by immune cells, such as myeloid cells and lym- yang et al. 2011; Rutz et al. 2014). phocytes (Rutz et al. 2014). Myeloid cells are the IL-10 was initially described as a secreted primary source for IL-19, IL-20, and IL-24 cytokine synthesis inhibitory factor (CSIF) pro- (Wolk et al. 2002). Epithelial cells, the main tar- duced by T helper (Th)2 T-cell clones with the get cells of IL-20 family cytokines, also produce ability to inhibit the production of Th1 cyto- IL-19, IL-20, and IL-24 in response to cytokines Editors: Warren J. Leonard and Robert D. Schreiber Additional Perspectives on Cytokines available at www.cshperspectives.org Copyright © 2019 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a028548 Cite this article as Cold Spring Harb Perspect Biol 2019;11:a028548 1 Downloaded from http://cshperspectives.cshlp.org/ on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press X. Wang et al. IL-22 IL-19 IL-28A IL-22BP IL-20 IL-20 IL-28B IL-10 IL-22 IL-24 IL-24 IL-26 IL-29 IL-22RA1 IL-22RA1 IL-10RB IL-20RB IL-10RB IL-20RA IL-20RB IL-20RA IL-10RA IL-28RA IL-10RB IL-10RB IL-10 IL-22 IL-20 receptor IL-20 receptor IL-26 IL-28 receptor receptor type 1 type 2 receptor receptor Figure 1. Interleukin (IL)-10 family cytokines and their receptors. secreted by immune cells (Hunt et al. 2006; Sa et uses IL-10RA, whereas IL-19, IL-20, and IL-24 al. 2007; Wolk et al. 2009b). T cells are a primary use IL-20RA as receptor α-subunits. IL-22 binds source for IL-22, IL-24, and IL-26. Additionally, IL-22RA1, which can also be bound by IL-20 IL-22 is produced by various other lymphoid and IL-24, collectively defining the IL-20 sub- populations, including γδ-T cells, NK cells, family. IL-28A, IL-28B, and IL-29, on the other and innate lymphoid cells (ILCs) (Rutz et al. hand, use a unique IL-28RA subunit. In addition 2013, 2014). Finally, both leukocytes and epithe- to these membrane-bound receptors, a soluble lial cells are major sources of IFN-λ family cy- form of the IL-22 receptor (IL-22BP or IL- tokines (Fig. 1) (Kotenko et al. 2003; Sheppard 22RA2) with homology to the extracellular do- et al. 2003; Uzé and Monneron 2007). main of IL-22RA1, binds IL-22 with high affinity Although the biological functions of the and blocks its activity (Ouyang et al. 2011; Rutz other IL-10 family cytokines are quite distinct et al. 2014). from IL-10 itself, all family members share sig- IL-10 family receptors signal through Janus nificant structural homology, having evolved tyrosine kinases (JAKs) and signal transducers through gene duplication. Most IL-10 family cy- and activators of transcription (STATs). Recep- tokines form homodimers, whereas some family tor α-subunits are constitutively associated with members, such as IL-22, exist in a monomeric Jak1, whereas Jak2 or Tyk2 are bound to the β- form. IL-10 family cytokines signal through het- subunits. Ligand binding initiates recruitment erodimeric receptors, composed of class II re- and phosphorylation of STATs, which in turn ceptor α- and β-subunits (Pestka et al. 2004). form homo- and heterodimers that translocate The prototypical class II receptor structure con- into the nucleus to induce transcription. IL-10 sists of tandem β–sheet-rich immunoglobulin and the IL-20 subfamily cytokines signal pri- (Ig)-like domains with fibronectin type III con- marily through STAT3 and STAT1, whereas nectivity. The α-receptor subunits show higher IL-28A, IL-28B, and IL-29 activate the ISGF3 affinity for the cytokine ligand than the β-sub- complex (Pestka et al. 2004; Ouyang et al. units. Interestingly, the receptor-binding mode 2011; Rutz et al. 2014). is virtually identical for monomeric or dimeric Distinct receptor expression patterns drive IL-10 family cytokines (Pestka et al. 2004). the diverse biology of IL-10 family cytokines The shared usage of common receptor sub- (Fig. 1). The IL-10RB β-subunit is ubiquitously units is a defining feature of the IL-10 cytokine expressed throughout the body, whereas expres- family (Fig. 1). All members bind either the IL- sion of the IL-20RB β-subunit is more restricted. 10RB or IL-20RB β-receptor subunits in combi- IL-10RA is mainly expressed on leukocytes. In nation with varying α-subunits. IL-10 uniquely contrast, IL-20 subfamily receptors showa rather 2 Cite this article as Cold Spring Harb Perspect Biol 2019;11:a028548 Downloaded from http://cshperspectives.cshlp.org/ on September 25, 2021 - Published by Cold Spring Harbor Laboratory Press Targeting IL-10 Family Cytokines to Treat Diseases restricted expression pattern. In particular the α- IL-10 also has stimulatory effects on CD8+ T receptor subunits, IL-20RA and IL-22RA1, are cells, and augments their proliferation and cyto- preferentially expressed on epithelial cells and toxic activity (Groux et al. 1998; Mumm et al. fibroblasts, but absent from hematopoietic cells 2011). It enhances the survival of human B cells (Aggarwal et al. 2001; Blumberg et al. 2001; Wolk and promotes B-cell proliferation (Levy and et al. 2002). IL-22RA1 is highly expressed in the Brouet 1994; Itoh and Hirohata 1995) and con- skin, pancreas, kidney, lung, intestine, and liver. tributes to the differentiation of B cells and their IL-20RA is expressed in the skin, lung, ovary, production and isotype switch of antibodies testes, and placenta, and at lower levels in the (Rousset et al. 1992). intestine and liver (Rutz et al. 2013, 2014). The Role of IL-10 in Inflammatory Bowel TARGETING IL-10 FOR THE TREATMENT Disease OF HUMAN AUTOIMMUNE DISEASES Given its multiple anti-inflammatory functions, As a major immune regulatory cytokine, IL-10 it is not surprising that IL-10 exerts essential can be produced by many leukocyte subsets and regulatory roles in many human autoimmune is under the control of various signal transduc- diseases. Inflammatory bowel disease (IBD) tion pathways and transcriptional networks comprises ulcerative colitis (UC) and Crohn’s (Saraiva and O’Garra 2010; Rutz and Ouyang disease (CD), both of which show uncontrolled 2011, 2016). According to the expression of its inflammation in the intestinal tract but differ in receptor, IL-10 acts on many cells of the immune pathophysiology. Mice deficient in either IL-10 system (Fig. 2), where it has profound anti-in- or the IL-10 receptor α or β chains develop flammatory functions (Moore et al. 2001; Rutz spontaneous colitis (Kühn et al. 1993), which is and Ouyang 2011). IL-10 mainly targets anti- dependent on the presence of the intestinal mi- gen-presenting cells (APCs), such as monocytes crobiota and involves the up-regulation of IL-23 and macrophages, and inhibits their release of (Sellon et al. 1998; Yen et al. 2006). Exogenously proinflammatory cytokines, such as tumor ne- provided recombinant IL-10 can delay and at- crosis factor α (TNF-α), IL-1β, IL-6, IL-8, gran- tenuate colitis development in these IL-10-de- ulocyte colony-stimulating factor (G-CSF), and ficient mice.
Load more

Recommended publications
  • Cytokine Nomenclature
    RayBiotech, Inc. The protein array pioneer company Cytokine Nomenclature Cytokine Name Official Full Name Genbank Related Names Symbol 4-1BB TNFRSF Tumor necrosis factor NP_001552 CD137, ILA, 4-1BB ligand receptor 9 receptor superfamily .2. member 9 6Ckine CCL21 6-Cysteine Chemokine NM_002989 Small-inducible cytokine A21, Beta chemokine exodus-2, Secondary lymphoid-tissue chemokine, SLC, SCYA21 ACE ACE Angiotensin-converting NP_000780 CD143, DCP, DCP1 enzyme .1. NP_690043 .1. ACE-2 ACE2 Angiotensin-converting NP_068576 ACE-related carboxypeptidase, enzyme 2 .1 Angiotensin-converting enzyme homolog ACTH ACTH Adrenocorticotropic NP_000930 POMC, Pro-opiomelanocortin, hormone .1. Corticotropin-lipotropin, NPP, NP_001030 Melanotropin gamma, Gamma- 333.1 MSH, Potential peptide, Corticotropin, Melanotropin alpha, Alpha-MSH, Corticotropin-like intermediary peptide, CLIP, Lipotropin beta, Beta-LPH, Lipotropin gamma, Gamma-LPH, Melanotropin beta, Beta-MSH, Beta-endorphin, Met-enkephalin ACTHR ACTHR Adrenocorticotropic NP_000520 Melanocortin receptor 2, MC2-R hormone receptor .1 Activin A INHBA Activin A NM_002192 Activin beta-A chain, Erythroid differentiation protein, EDF, INHBA Activin B INHBB Activin B NM_002193 Inhibin beta B chain, Activin beta-B chain Activin C INHBC Activin C NM005538 Inhibin, beta C Activin RIA ACVR1 Activin receptor type-1 NM_001105 Activin receptor type I, ACTR-I, Serine/threonine-protein kinase receptor R1, SKR1, Activin receptor-like kinase 2, ALK-2, TGF-B superfamily receptor type I, TSR-I, ACVRLK2 Activin RIB ACVR1B
    [Show full text]
  • Overlapping, Additive and Counterregulatory Effects of Type II and I Interferons on Myeloid Dendritic Cell Functions
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Serveur académique lausannois Review Article TheScientificWorldJOURNAL (2011) 11, 2071–2090 ISSN 1537-744X; doi:10.1100/2011/873895 Overlapping, Additive and Counterregulatory Effects of Type II and I Interferons on Myeloid Dendritic Cell Functions Loredana Frasca and Roberto Lande Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanita,` 00161 Rome, Italy Received 8 April 2011; Accepted 27 September 2011 Academic Editor: Fulvio D’Acquisto Dendritic cells (DCs) are central player in immunity by bridging the innate and adaptive arms of the immune system (IS). Interferons (IFNs) are one of the most important factors that regulate both innate and adaptive immunity too. Thus, the understanding of how type II and I IFNs modulate the immune-regulatory properties of DCs is a central issue in immunology. In this paper, we will address this point in the light of the most recent literature, also highlighting the controversial data reported in the field. According to the wide literature available, type II as well as type I IFNs appear, at the same time, to collaborate, to induce additive effects or overlapping functions, as well as to counterregulate each one’s effects on DC biology and, in general, the immune response. The knowledge of these effects has important therapeutic implications in the treatment of infec- tious/autoimmune diseases and cancer and indicates strategies for using IFNs as vaccine adju- vants and in DC-based immune therapeutic approaches. KEYWORDS: IFNs, dendritic cell effector functions, immune activation, immune regulation, cross- regulation Correspondence should be addressed to Loredana Frasca, [email protected] Copyright © 2011 L.
    [Show full text]
  • Cyclooxygenase-2 Inflammatory Factors, IL-29, IL-8, And
    Hepatitis B Virus Induces a Novel Inflammation Network Involving Three Inflammatory Factors, IL-29, IL-8, and Cyclooxygenase-2 This information is current as of September 27, 2021. Yi Yu, Rui Gong, Yongxin Mu, Yanni Chen, Chengliang Zhu, Zhichen Sun, Mingzhou Chen, Yingle Liu, Ying Zhu and Jianguo Wu J Immunol 2011; 187:4844-4860; Prepublished online 28 September 2011; Downloaded from doi: 10.4049/jimmunol.1100998 http://www.jimmunol.org/content/187/9/4844 http://www.jimmunol.org/ References This article cites 55 articles, 29 of which you can access for free at: http://www.jimmunol.org/content/187/9/4844.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 27, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Hepatitis B Virus Induces a Novel Inflammation Network Involving Three Inflammatory Factors, IL-29, IL-8, and Cyclooxygenase-2 Yi Yu,*,†,‡ Rui Gong,*,† Yongxin Mu,*,† Yanni Chen,*,†,‡ Chengliang Zhu,*,† Zhichen Sun,*,† Mingzhou Chen,*,†,‡ Yingle Liu,*,†,‡ Ying Zhu,*,†,‡ and Jianguo Wu*,†,‡ Chronic inflammation induced by hepatitis B virus (HBV) is a major causative factor associated with the development of cirrhosis and hepatocellular carcinoma.
    [Show full text]
  • HUMAN INTERLEUKIN-29/INTERFERON-LAMBDA 1 Product Number: 11825-1 Lot Number: 5620 Expiration Date: October 2, 2013 Size: 25 Μg
    HUMAN INTERLEUKIN-29/INTERFERON-LAMBDA 1 Product Number: 11825-1 Lot Number: 5620 Expiration Date: October 2, 2013 Size: 25 μg Description: Human Interleukin-29/Interferon-Lambda 1 Source: DNA sequence encoding the signal peptide from human CD33 was fused to the carboxyl terminally polyhistidine-tagged mature human IL-29 (Gly 20 - Thr 200) (Sheppard, P. et al., 2003, Nat. Immunol. 4(1):63 - 68). The chimeric protein was expressed in a mouse myeloma cell line, NS0. Form: Lyophilized Buffer: Phosphate-buffered saline (PBS) containing 50μg of bovine serum albumin (BSA) per 1 μg of cytokine Reconstitution: It is recommended that sterile PBS containing at least 0.1% human serum albumin or bovine serum albumin be added to the vial to prepare a stock solution of no less than 10μg/ml. Endotoxin: < 1 EU/μg Molecular Weight: Based on N-terminal sequencing, the mature recombinant IL-29 starts at Gly 20 and has a calculated molecular mass of 21.4 kDa. As a result of glycosylation, the recombinant monomer migrates as an approximately 26-35kDa protein in SDS-PAGE under reducing conditions. Purity: > 95% Synonyms: Hu IL-29; Hu IFN-λ1 Assays Used to Measure Bioactivity: Human HepG2 cells infected with encephalomyocarditis virus (Sheppard, P. et al., 2003, Nature Immunol. 4:63). The ED50 for this effect is typically 1- 5 ng/mL. Shipping Conditions: Wet Ice Physical State of Product During Shipping: Lyophilized Special Conditions/Comments: After receipt, this product should be kept at -70˚C or below for retention of full activity. Upon reconstitution, this cytokine can be stored under sterile conditions at -20˚C to -70˚C in a manual defrost freezer for three months without detection loss of activity.
    [Show full text]
  • Cells 1/IL-29) in Human Airway Epithelial Λ (IFN- 1 Promoter Activity
    Regulation of IFN-λ1 Promoter Activity (IFN- λ1/IL-29) in Human Airway Epithelial Cells This information is current as Rachael Siegel, Joyce Eskdale and Grant Gallagher of September 27, 2021. J Immunol 2011; 187:5636-5644; Prepublished online 4 November 2011; doi: 10.4049/jimmunol.1003988 http://www.jimmunol.org/content/187/11/5636 Downloaded from References This article cites 48 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/187/11/5636.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 27, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Regulation of IFN-l1 Promoter Activity (IFN-l1/IL-29) in Human Airway Epithelial Cells Rachael Siegel, Joyce Eskdale, and Grant Gallagher The type III (l) IFNs (IFN-l1, IFN-l2, and IFN-l3) and their receptor are the most recently discovered IFN family.
    [Show full text]
  • Secreted Factors from Dental Pulp Stem Cells Improve Sjögren's Syndrome Via Regulatory T Cell-Mediated Immunosuppression
    Matsumura-Kawashima et al. Stem Cell Research & Therapy (2021) 12:182 https://doi.org/10.1186/s13287-021-02236-6 RESEARCH Open Access Secreted factors from dental pulp stem cells improve Sjögren’s syndrome via regulatory T cell-mediated immunosuppression Mayu Matsumura-Kawashima†, Kenichi Ogata*† , Masafumi Moriyama, Yuka Murakami, Tatsuya Kawado and Seiji Nakamura Abstract Background: Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily characterized by inflammation in the salivary and lacrimal glands. Activated T cells contribute to disease pathogenesis by producing proinflammatory cytokines, which leads to a positive feedback loop establishment. The study aimed to evaluate the effects of secreted factors derived from dental pulp stem cells (DPSCs) or bone marrow mesenchymal stem cells (BMMSCs) on hyposalivation in SS and to investigate the mechanism involved. Methods: Eighty percent confluent stem cells were replenished with serum-free Dulbecco’s modified Eagle’s medium and incubated for 48 h; following which, conditioned media from DPSCs (DPSC-CM) and BMMSCs (BMMSC-CM) were collected. Cytokine array analysis was performed to assess the types of cytokines present in the media. Flow cytometric analysis was performed to evaluate the number of activated T cells cultured in DPSC-CM or BMMSC-CM. Subsequently, DPSC-CM or BMMSC-CM was administered to an SS mouse model. The mice were categorized into the following groups (n = 6 each): non-treatment, Dulbecco’s modified Eagle’s medium (−), BMMSC-CM, and DPSC-CM. Histological analysis of the salivary glands was performed. The gene and protein expression levels of cytokines associated with T helper subsets in the submandibular glands (SMGs) were evaluated.
    [Show full text]
  • The Role of Il-29 and Il-28B in the Innate Immune Response
    THE ROLE OF IL-29 AND IL-28B IN THE INNATE IMMUNE RESPONSE Megumi A. Williamson A thesis submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Master of Science in the Department of Periodontology, School of Dentistry Chapel Hill 2018 Approved by: Thiago Morelli Thiago Morelli Julie Marchesan Steven Offenbacher Antonio Amelio ©2018 Megumi A. Williamson ALL RIGHTS RESERVED ii ABSTRACT Megumi A. Williamson: The Role of IL-29 and IL-28B in the Innate Immune Response (Under the direction of Thiago Morelli, Julie Marchesan, Steven Offenbacher, and Antonio Amelio) Aims: Chronic periodontitis (CP) is an inflammatory disease induced by dysbiotic biofilm in a susceptible host, resulting in progressive attachment loss, and subsequent alveolar bone loss. Recent genome-wide association studies (GWAS) and genome-wide gene centric analysis on periodontal complex traits (PCTs) identified possible associations of IL-29 and IL- 28B with periodontal diseases. However, the underlying mechanisms for how these genes contribute to the pathogenesis of periodontitis are largely unknown. The aims of the present study were to explore the role of IL-29 and IL-28B and their gene polymorphisms in the innate immune response by dendritic cells. Materials and methods: To explore the effect of IL-29 on the cytokine production in response to TLR4 stimulation, the IL-29 gene was knocked-down in THP-1 cells using IL-29 shRNA lentiviral particles. Pro- and anti-inflammatory cytokine levels were measured with Luminex® multiplex assay. To assess the effect of genetic variations in IL- 29 and IL-28B, whole blood samples from fifteen subjects (6 subjects with major allele for both IL-29 and IL-28B, 5 subjects for major allele in IL-29 and minor allele in IL-28B, and 4 subjects with minor alleles for both genes) were collected and CD14+/CD16lo PBMCs were isolated to generate DCs.
    [Show full text]
  • IL-1Β Induces the Rapid Secretion of the Antimicrobial Protein IL-26 From
    Published June 24, 2019, doi:10.4049/jimmunol.1900318 The Journal of Immunology IL-1b Induces the Rapid Secretion of the Antimicrobial Protein IL-26 from Th17 Cells David I. Weiss,*,† Feiyang Ma,†,‡ Alexander A. Merleev,x Emanual Maverakis,x Michel Gilliet,{ Samuel J. Balin,* Bryan D. Bryson,‖ Maria Teresa Ochoa,# Matteo Pellegrini,*,‡ Barry R. Bloom,** and Robert L. Modlin*,†† Th17 cells play a critical role in the adaptive immune response against extracellular bacteria, and the possible mechanisms by which they can protect against infection are of particular interest. In this study, we describe, to our knowledge, a novel IL-1b dependent pathway for secretion of the antimicrobial peptide IL-26 from human Th17 cells that is independent of and more rapid than classical TCR activation. We find that IL-26 is secreted 3 hours after treating PBMCs with Mycobacterium leprae as compared with 48 hours for IFN-g and IL-17A. IL-1b was required for microbial ligand induction of IL-26 and was sufficient to stimulate IL-26 release from Th17 cells. Only IL-1RI+ Th17 cells responded to IL-1b, inducing an NF-kB–regulated transcriptome. Finally, supernatants from IL-1b–treated memory T cells killed Escherichia coli in an IL-26–dependent manner. These results identify a mechanism by which human IL-1RI+ “antimicrobial Th17 cells” can be rapidly activated by IL-1b as part of the innate immune response to produce IL-26 to kill extracellular bacteria. The Journal of Immunology, 2019, 203: 000–000. cells are crucial for effective host defense against a wide and neutrophils.
    [Show full text]
  • Evolutionary Divergence and Functions of the Human Interleukin (IL) Gene Family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W
    UPDATE ON GENE COMPLETIONS AND ANNOTATIONS Evolutionary divergence and functions of the human interleukin (IL) gene family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W. Nebert3* and Vasilis Vasiliou1 1Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA 2Department of Clinical Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA 3Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH 45267–0056, USA *Correspondence to: Tel: þ1 513 821 4664; Fax: þ1 513 558 0925; E-mail: [email protected]; [email protected] Date received (in revised form): 22nd September 2010 Abstract Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term ‘interleukin’ (IL) has been used to describe a group of cytokines with complex immunomodulatory functions — including cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing cell type, the responding cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host’s immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating cell type.
    [Show full text]
  • Recombinant Human Cytokines
    HOME recombinant human cytokines rh 4-1BBL / CD137L (4-1BB Ligand) Catalog# Biol.Activity Size Price 11345180 5 – 10 ng/ml 5 µg 49 EUR 11345184 5 – 10 ng/ml 20 µg 139 EUR rh 4-1BBR / CD137 (4-1BB Receptor) Catalog# Biol.Activity Size Price 11344120 90% inhibition using 1µg 5 µg 49 EUR 11344124 90% inhibition using 1µg 20 µg 139 EUR rh Activin A active (source Nicotiana benthamiana) Catalog# Biol.Activity Size Price 11344471 < 5 ng/ml 1 µg 42 EUR 11344470 < 5 ng/ml 5 µg 89 EUR 11344474 < 5 ng/ml 25 µg 199 EUR 11344476 < 5 ng/ml 100 µg 599 EUR rh Activin A (source E.coli) Catalog# Biol.Activity Size Price 11344962 2 µg 49 EUR 11344963 10 µg 129 EUR rh Activin B active (source Nicotiana benthamiana) Catalog# Biol.Activity Size Price 11345252 2 µg 39 EUR 11345253 10 µg 149 EUR rh Acrp30 HEK (Adiponectin HEK derived) Catalog# Biol.Activity Size Price 11344462 6 µg/ml 2 µg 49 EUR 11344463 6 µg/ml 10 µg 139 EUR rh AREG (Amphiregulin) Catalog# Biol.Activity Size Price 11344803 5 -10 ng/ml 10 µg 49 EUR 11344805 5 -10 ng/ml 50 µg 139 EUR rh Artemin Catalog# Biol.Activity Size Price 11343772 4 - 8 ng/ml 2 µg 39 EUR rh BAFF / CD257 (B- Lymphocyte Stimulator) Catalog# Biol.Activity Size Price 11343430 10 ng/ml 5 µg 49 EUR 11343434 10 ng/ml 20 µg 99 EUR 11343436 10 ng/ml 100 µg 379 EUR rh BAFF-R / CD268 (B-Lymphocyte Stimulator Receptor / TNFRSF13C) Catalog# Biol.Activity Size Price 11344440 1.0 - 5.0 µg/ml 5 µg 49 EUR 11344444 1.0 - 5.0 µg/ml 20 µg 139 EUR HOME recombinant human cytokines rh BCA-1 (CXCL13) Catalog# Biol.Activity Size Price 11344180
    [Show full text]
  • Full-Text.Pdf
    IL-17A Attenuates IFN-λ Expression by Inducing Suppressor of Cytokine Signaling Expression in Airway Epithelium This information is current as Mitsuru Niwa, Tomoyuki Fujisawa, Kazutaka Mori, of September 28, 2021. Katsumasa Yamanaka, Hideki Yasui, Yuzo Suzuki, Masato Karayama, Hironao Hozumi, Kazuki Furuhashi, Noriyuki Enomoto, Yutaro Nakamura, Naoki Inui, Tetsuro Suzuki, Masato Maekawa and Takafumi Suda J Immunol published online 17 September 2018 Downloaded from http://www.jimmunol.org/content/early/2018/09/14/jimmun ol.1800147 Supplementary http://www.jimmunol.org/content/suppl/2018/09/14/jimmunol.180014 http://www.jimmunol.org/ Material 7.DCSupplemental Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 28, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2018 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published
    [Show full text]
  • NIH Public Access Author Manuscript Curr Opin Virol
    NIH Public Access Author Manuscript Curr Opin Virol. Author manuscript; available in PMC 2012 December 1. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Curr Opin Virol. 2011 December 1; 1(6): 476±486. doi:10.1016/j.coviro.2011.11.001. Induction and Function of Type I and III Interferon in Response to Viral Infection David E. Levy*, Isabelle J. Marié, and Joan E. Durbin Departments of Pathology and Microbiology, NYU School of Medicine, 550 1st Ave, New York NY 10016 USA Abstract The type I and III interferon (IFN) families consist of cytokines rapidly induced during viral infection that confer antiviral protection on target cells and are critical components of innate immune responses and the transition to effective adaptive immunity. The regulation of their expression involves an intricate and stringently regulated signaling cascade, initiated by recognition most often of viral nucleic acid in cytoplasmic and endosomal compartments and involving a series of protein conformational rearrangements and interactions regulated by helicase action, ubiquitin modification, and protein aggregation, culminating in kinase activation and phosphorylation of critical transcription factors and their regulators. The many IFN subtypes induced by viruses confer amplification, diversification, and cell-type specificity to the host response to infection, providing fertile ground for development of antiviral therapeutics and vaccines. Introduction Type I and type III interferon (IFN) are a diverse family of cytokines, related by structure, regulation, and function. In humans and most mammals, the classical type I IFN proteins are encoded by a single IFN-β gene, a dozen or so IFN-α genes, plus various more distantly related genes and pseudogenes for IFN-ε, κ, τ, δ, ζ, ω, and v, depending on species.
    [Show full text]