DOCSLIB.ORG

Macrophages Via Effects on NK Cells, CD4 T Cells, and Drastically Alters

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Macrophages Via Effects on NK Cells, CD4 T Cells, and Drastically Alters The Absence or Overexpression of IL-15 Drastically Alters Breast Cancer Metastasis via Effects on NK Cells, CD4 T Cells, and Macrophages This information is current as of September 25, 2021. Amy Gillgrass, Navkiran Gill, Artem Babian and Ali A. Ashkar J Immunol published online 29 October 2014 http://www.jimmunol.org/content/early/2014/10/29/jimmun ol.1303175 Downloaded from Why The JI? Submit online. http://www.jimmunol.org/ • 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 *average by guest on September 25, 2021 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 © 2014 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published October 29, 2014, doi:10.4049/jimmunol.1303175 The Journal of Immunology The Absence or Overexpression of IL-15 Drastically Alters Breast Cancer Metastasis via Effects on NK Cells, CD4 T Cells, and Macrophages Amy Gillgrass, Navkiran Gill, Artem Babian, and Ali A. Ashkar IL-15 is a cytokine that can affect many immune cells, including NK cells and CD8 T cells. In several tumor models, IL-15 delays primary tumor formation and can prevent or reduce metastasis. In this study, we have employed a model of breast cancer metastasis to examine the mechanism by which IL-15 affects metastasis. When breast tumor cells were injected i.v. into IL-152/2, C57BL/6, IL- 15 transgenic (TG) and IL-15/IL-15Ra–treated C57BL/6 mice, there were high levels of metastasis in IL-152/2 mice and virtually no metastasis in IL-15 TG or IL-15–treated mice. In fact, IL-152/2 mice were 10 times more susceptible to metastasis, whereas IL- 15 TG mice were at least 10 times more resistant to metastasis when compared with control C57BL/6 mice. Depletion of NK cells Downloaded from from IL-15 TG mice revealed that these cells were important for protection from metastasis. When NK cells were depleted from control C57BL/6 mice, these mice did not form as many metastatic foci as IL-152/2 mice, suggesting that other cell types may be contributing to metastasis in the absence of IL-15. We then examined the role of CD4 T cells and macrophages. In IL-152/2 mice, in vivo depletion of CD4 T cells decreased metastasis. The lack of IL-15 in IL-152/2 mice, and possibly the Th2-polarized CD4 T cells, was found to promote the formation of M2 macrophages that are thought to contribute to metastasis formation. This study reveals that whereas IL-15 effects on NK cells are important, it also has effects on other immune cells that contribute to http://www.jimmunol.org/ metastasis. The Journal of Immunology, 2014, 193: 000–000. nterleukin-15 is a cytokine that has effects on cells of the promote tumor cell death due to their production of NO, proin- innate and adaptive immune system. It is most known for its flammatory cytokines, efficient Ag presentation, and phagocytic I effects in promoting the survival, differentiation, and acti- abilities (10, 11). In contrast, the alternatively activated group of vation of NK cells, as well as promoting memory CD8 T cell macrophages (M2), of which tumor-associated macrophages responses (1–3). Because both NK cells and CD8 T cells are (TAMs) are a member, has more of a role in tumor promotion (10, important in tumor defense and correlate with survival in various 12). It functions to promote angiogenesis, tumor cell invasion, and cancers, there has been extensive interest in IL-15 as an immu- intravasation, and it plays a role at the metastatic site (11). by guest on September 25, 2021 notherapy (4–6). The effects of IL-15 have been assessed in many Macrophages are very plastic and are able to travel between M1 tumor models, and it has been found to be effective against pri- and M2 states depending on the microenvironment in which they mary tumors as well as metastasis (7–9). In many cases, the are found (13). M1 macrophages are created in environments with mechanism of protection from metastasis was not evaluated. stimuli such as IFN-g and LPS (14). M2 is a group of macro- When investigated in models of metastasis, NK cells were most phages that can develop under the influence of IL-4/IL-13, im- frequently the cell type identified that was important for protection mune complexes, IL-10, TGF-b, or glucocorticoids (14). (7, 9). Although the role of macrophages at the primary tumor is well In recent years, it has become apparent that macrophages are established, a lot less attention has been paid to the role of mac- very important cell types involved in the promotion of metastasis. rophages at the metastatic site. Kaplan et al. (15) found that after Classically activated macrophages, also known as M1, are able to primary tumors have been established, but before metastasis has occurred, there are premetastatic sites in which there are clusters of vascular endothelial growth factor receptor+ hematopoietic Department of Pathology and Molecular Medicine, McMaster Immunology Research + Center, McMaster University, Hamilton, Ontario L8N 3Z5, Canada bone marrow progenitors. CD11b myeloid cells are also attracted Received for publication November 27, 2013. Accepted for publication October 5, to these premetastatic niches, and these cells are important for 2014. establishing metastasis (16). Recently, to investigate the role of This work was supported by grants from the Canadian Breast Cancer Foundation. macrophages at the metastatic site, several groups have used the A.G. was the recipient of Ph.D. fellowships from the Canadian Institutes for Health injection of tumor cells i.v. to mimic tumor metastasis. In models Research and the Canadian Breast Cancer Foundation; N.G. was awarded an Ontario Graduate Scholarship; and A.A.A. was the recipient of Canada’s Research-Based such as this, macrophages are required for efficient tumor cell Pharmaceutical Companies/Canadian Institutes for Health Research Career Award seeding as well as growth at the metastatic site (17, 18). in Health Research. Macrophage polarization is dependent upon the signals it The PCR array presented in this article has been submitted to the Gene Expression receives in its microenvironment. It is, of course, no wonder that Omnibus (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE61858) under ac- cession number GSE61858. CD4 T cells play a role in macrophage polarization. Th1 CD4 Address correspondence and reprint requests to Dr. Ali A. Ashkar, McMaster Uni- T cells produce IFN-g, which promotes M1 macrophage polari- versity, 1280 Main Street West, MDCL 4074, Hamilton, ON L8N 3Z5, Canada. zation, whereas Th2 or regulatory T cells produce IL-10, IL-4, or E-mail address: [email protected] IL-13, which promotes M2 macrophage polarization (19). In fact, Abbreviations used in this article: MT, middle T; TAM, tumor-associated macro- in mouse models that are Th2 biased, knockout of CD4 T cells phage; TG, transgenic. promotes the formation of macrophages with a more M1 pheno- Copyright Ó 2014 by The American Association of Immunologists, Inc. 0022-1767/14/$16.00 type (20, 21). Macrophages also influence the polarization of www.jimmunol.org/cgi/doi/10.4049/jimmunol.1303175 2 THE EFFECTS OF IL-15 ON BREAST CANCER METASTASIS T cells themselves, with M2 macrophages promoting the forma- in PBS and resuspended as 0.5 3 106–1 3 106 per 400 ml sterile PBS. Cells 2/2 tion of T regulatory cells (22). Recently, it was discovered that, in with ,5% cell death were injected via the tail vein of IL-15 , C57BL/6, or a spontaneous model of breast tumor formation, CD4 T cells IL-15 TG mice. Mice were monitored for endpoint, and 13 d postinjection, mice were euthanized and lungs were harvested. Lungs were fixed in 2% expressing IL-4 were able to promote invasion and metastasis paraformaldehyde for 48 h. Sections were then stained with H&E for analysis due to their effects on promoting M2 phenotype in TAMs (20). In of lung tumor metastasis. The level of metastasis was assessed while blinded this case, loss of CD4 T cells actually decreased the amount of in ImageJ. In brief, in an entire lobe of lung, per each experimental animal, metastasis observed (20). Other studies have also indicated that a threshold algorithm was applied to assess tumor area (manually checked for accuracy). Total lung area (with lumen areas subtracted) was also assessed, CD4 T cells may play a role in promoting metastasis, although via and percentage of tumor area was calculated by the following formula: different mechanisms (23, 24). The effect of IL-15 on macrophages and CD4 T cells is an area Percent tumor area ¼ðtumor area=total lung areaÞ 3 100 that has not been studied thoroughly. It is known that IL-15 is Melanoma cells (B16F10) were also used and were prepared in the same produced from human monocytes upon LPS activation (25). manner as MT cells. A total of 1 3 105 cells was injected in the tail vein of Several in vitro studies on various sources of macrophages IL-152/2 and C57BL/6 control mice.
Load more

Recommended publications
  • Rescuing Functional T Cells Induced by Growth Factor Deprivation, CCL2 Inhibits the Apoptosis Program
    CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells This information is current as Eva Diaz-Guerra, Rolando Vernal, M. Julieta del Prete, of September 24, 2021. Augusto Silva and Jose A. Garcia-Sanz J Immunol 2007; 179:7352-7357; ; doi: 10.4049/jimmunol.179.11.7352 http://www.jimmunol.org/content/179/11/7352 Downloaded from References This article cites 41 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/179/11/7352.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 24, 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 © 2007 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology CCL2 Inhibits the Apoptosis Program Induced by Growth Factor Deprivation, Rescuing Functional T Cells1 Eva Diaz-Guerra,2 Rolando Vernal,2 M. Julieta del Prete,2 Augusto Silva, and Jose A. Garcia-Sanz3 The precise mechanisms involved in the switch between the clonal expansion and contraction phases of a CD8؉ T cell response remain to be fully elucidated.
    [Show full text]
  • Interleukin-15-Mediated Immunotoxicity and Exacerbation of Sepsis
    INTERLEUKIN-15-MEDIATED IMMUNOTOXICITY AND EXACERBATION OF SEPSIS: ROLE OF NATURAL KILLER CELLS AND INTERFERON γ By Yin Guo Dissertation Submitted to the Faculty of the Graduate School of Vanderbilt University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in Microbiology and Immunology December 2016 Nashville, Tennessee Approved Luc Van Kaer, Ph.D. Stokes Peebles, M.D. Lorraine Ware, M.D. Daniel Moore, M.D., Ph.D. Edward Sherwood, M.D, Ph.D. i Copyright © 2016 by Yin Guo All Rights Reserved ii ACKNOWLEDGEMENTS I would like to thank my thesis mentor, Dr. Edward Sherwood for his tremendous instruction and support during my entire Ph.D. training course. I joined Dr. Sherwood’s lab in the department of Microbiology and Immunology of University of Texas Medical Branch (UTMB) at Galveston in 2011. I appreciated the offer Dr. Sherwood provided to move to Vanderbilt University together. During the new lab setup period, he gave me a lot of encouragement about going out to meet students and professors at the Pathology, Microbiology and Immunology Department. From making new friends in our department, I started to know a lot of useful information and resources about how to adapt to new life in Nashville and how to prepare for the qualifying exam. Dr. Sherwood is a highly responsible and enthusiastic mentor although he has busy medical practice in the operating room and needs to write many grants. I have to say, he is the most diligent person I have seen in the world. It is amazing to me that he never seems to be exhausted or desensitized with reviewing our papers, reading papers, writing grants, and discussing data and new ideas.
    [Show full text]
  • Metamorphic Protein Folding Encodes Multiple Anti-Candida Mechanisms in XCL1
    pathogens Article Metamorphic Protein Folding Encodes Multiple Anti-Candida Mechanisms in XCL1 Acacia F. Dishman 1,2,†, Jie He 3,†, Brian F. Volkman 1,* and Anna R. Huppler 3,* 1 Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA; [email protected] 2 Medical Scientist Training Program, Medical College of Wisconsin, Milwaukee, WI 53226, USA 3 Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA; [email protected] * Correspondence: [email protected] (B.F.V.); [email protected] (A.R.H.) † These authors contributed equally. Abstract: Candida species cause serious infections requiring prolonged and sometimes toxic therapy. Antimicrobial proteins, such as chemokines, hold great interest as potential additions to the small number of available antifungal drugs. Metamorphic proteins reversibly switch between multiple different folded structures. XCL1 is a metamorphic, antimicrobial chemokine that interconverts between the conserved chemokine fold (an α–β monomer) and an alternate fold (an all-β dimer). Previous work has shown that human XCL1 kills C. albicans but has not assessed whether one or both XCL1 folds perform this activity. Here, we use structurally locked engineered XCL1 variants and Candida killing assays, adenylate kinase release assays, and propidium iodide uptake assays to demonstrate that both XCL1 folds kill Candida, but they do so via different mechanisms. Our results suggest that the alternate fold kills via membrane disruption, consistent with previous work, and the chemokine fold does not. XCL1 fold-switching thus provides a mechanism to regulate Citation: Dishman, A.F.; He, J.; the XCL1 mode of antifungal killing, which could protect surrounding tissue from damage associ- Volkman, B.F.; Huppler, A.R.
    [Show full text]
  • Lymphotactin Mediates Antiviral T Cell Trafficking Within
    LYMPHOTACTIN MEDIATES ANTIVIRAL T CELL TRAFFICKING WITHIN THE CENTRAL NERVOUS SYSTEM DURING WEST NILE VIRUS ENCEPHALITIS A Thesis Presented to the Faculty of California State Polytechnic University, Pomona In Partial Fulfillment Of the Requirements for the Degree Master of Science In Biological Sciences By Sharese Tronti 2019 SIGNATURE PAGE THESIS: LYMPHOTACTIN MEDIATES ANTIVIRAL T CELL TRAFFICKING WITHIN THE CENTRAL NERVOUS SYSTEM DURING WEST NILE VIRUS ENCEPHALITIS AUTHOR: Sharese Tronti DATE SUBMITTED: Spring 2019 Department of Biological Sciences Dr. Douglas Durrant Thesis Committee Chair Biological Sciences Dr. Andrew Steele Biological Sciences Dr. Jamie Snyder Biological Science ii ABSTRACT West Nile Virus (WNV), a neurotropic flavivirus, can cause neuroinvasive disease in humans. After peripheral infection, WNV is able to enter the central nervous system (CNS) and infect neurons causing neuronal injury and inflammation that potentially may result in fatality. In order to restrict viral replication and pathogenesis within the CNS during WNV encephalitis, virus-specific CD8+ T cells are critically dependent on dendritic cell (DC) mediated reactivation at this site. However, the mechanism by which DCs are recruited to the brain to ensure their interaction with infiltrating virus-specific CD8+ T cells remains unknown. Previous studies have demonstrated that, upon activation, CD8+ T cells rapidly produce the chemokine lymphotactin when activated. The receptor for lymphotactin, XCR1, is exclusively expressed on a subset of DCs, CD8+ DCs, which have been shown to be essential in establishing protective peripheral immunity against viruses and intracellular bacteria. In this study, we show that lymphotactin regulates the CNS entry of T lymphocytes, potentially promoting virologic control within the CNS and limiting neuronal cell death.
    [Show full text]
  • Single-Cell Landscape of Bronchoalveolar Immune Cells in Patients with COVID-19
    BRIEF COMMUNICATION https://doi.org/10.1038/s41591-020-0901-9 Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19 Mingfeng Liao1,6, Yang Liu1,6, Jing Yuan2,6, Yanling Wen1, Gang Xu1, Juanjuan Zhao1, Lin Cheng1, Jinxiu Li2, Xin Wang1, Fuxiang Wang2, Lei Liu1,3 ✉ , Ido Amit 4 ✉ , Shuye Zhang 5 ✉ and Zheng Zhang 1,3 ✉ Respiratory immune characteristics associated with The macrophage compartments differed largely in both compo- Coronavirus Disease 2019 (COVID-19) severity are cur- sition and expression of FCN1, SPP1 and FABP4 in different cell rently unclear. We characterized bronchoalveolar lavage fluid groups (Fig. 1c and Extended Data Fig. 2d). FABP4 was prefer- immune cells from patients with varying severity of COVID-19 entially expressed by controls and patients with moderate infec- and from healthy people by using single-cell RNA sequencing. tion, while FCN1 and SPP1 were highly expressed by patients Proinflammatory monocyte-derived macrophages were abun- with severe/critical infection (Fig. 1d). We conducted differen- dant in the bronchoalveolar lavage fluid from patients with tially expressed gene (DEG) analysis (Extended Data Fig. 2e), gene severe COVID-9. Moderate cases were characterized by the ontology (GO) analysis and gene set enrichment analysis (GSEA) presence of highly clonally expanded CD8+ T cells. This atlas (Extended Data Fig. 2f) between cell groups. Group 1 expressed of the bronchoalveolar immune microenvironment suggests the peripheral monocyte-like markers S100A8, FCN1 and CD14, potential mechanisms underlying pathogenesis and recovery and group 2 expressed high levels of the chemokines CCL2, CCL3, in COVID-19. CXCL10 and other genes.
    [Show full text]
  • COMPREHENSIVE INVITED REVIEW Chemokines and Their Receptors
    COMPREHENSIVE INVITED REVIEW Chemokines and Their Receptors Are Key Players in the Orchestra That Regulates Wound Healing Manuela Martins-Green,* Melissa Petreaca, and Lei Wang Department of Cell Biology and Neuroscience, University of California, Riverside, California. Significance: Normal wound healing progresses through a series of over- lapping phases, all of which are coordinated and regulated by a variety of molecules, including chemokines. Because these regulatory molecules play roles during the various stages of healing, alterations in their presence or function can lead to dysregulation of the wound-healing process, potentially leading to the development of chronic, nonhealing wounds. Recent Advances: A discovery that chemokines participate in a variety of disease conditions has propelled the study of these proteins to a level that potentially could lead to new avenues to treat disease. Their small size, ex- posed termini, and the fact that their only modifications are two disulfide Manuela Martins-Green, PhD bonds make them excellent targets for manipulation. In addition, because they bind to G-protein-coupled receptors (GPCRs), they are highly amenable to Submitted for publication January 9, 2013. *Correspondence: Department of Cell Biology pharmacological modulation. and Neuroscience, University of California, Riv- Critical Issues: Chemokines are multifunctional, and in many situations, their erside, Biological Sciences Building, 900 Uni- functions are highly dependent on the microenvironment. Moreover, each versity Ave., Riverside, CA 92521 (email: [email protected]). specific chemokine can bind to several GPCRs to stimulate the function, and both can function as monomers, homodimers, heterodimers, and even oligo- mers. Activation of one receptor by any single chemokine can lead to desen- Abbreviations sitization of other chemokine receptors, or even other GPCRs in the same cell, and Acronyms with implications for how these proteins or their receptors could be used to Ang-2 = angiopoietin-2 manipulate function.
    [Show full text]
  • Aire-Dependent Production of XCL1 Mediates Medullary Accumulation of Thymic Dendritic Cells and Contributes to Regulatory T Cell Development
    Article Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development Yu Lei,1,3 Adiratna Mat Ripen,1 Naozumi Ishimaru,2 Izumi Ohigashi,1 Takashi Nagasawa,4 Lukas T. Jeker,5 Michael R. Bösl,6 Georg A. Holländer,5 Yoshio Hayashi,2 Rene de Waal Malefyt,7 Takeshi Nitta,1 and Yousuke Takahama1 1Division of Experimental Immunology, Institute for Genome Research, 2Department of Oral Molecular Pathology, Institute of Health Biosciences, University of Tokushima, Tokushima 770-8503, Japan 3Key Laboratory of Molecular Biology for Infectious Disease of the People’s Republic of China Ministry of Education, Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China 4Department of Immunobiology and Hematology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan 5Laboratory of Pediatric Immunology, Center for Biomedicine, University of Basel and The University Children’s Hospital of Basel, 4058 Basel, Switzerland 6 Transgenic Core Facility, Max-Planck-Institute of Biochemistry, 82152 Martinsried, Germany 7Merck Research Laboratories, Palo Alto, CA 94304 Dendritic cells (DCs) in the thymus (tDCs) are predominantly accumulated in the medulla and contribute to the establishment of self-tolerance. However, how the medullary accu- mulation of tDCs is regulated and involved in self-tolerance is unclear. We show that the chemokine receptor XCR1 is expressed by tDCs, whereas medullary thymic epithelial cells (mTECs) express the ligand XCL1. XCL1-deficient mice are defective in the medullary accumulation of tDCs and the thymic generation of naturally occurring regulatory T cells (nT reg cells). Thymocytes from XCL1-deficient mice elicit dacryoadenitis in nude mice.
    [Show full text]
  • 359.Full.Pdf
    359 Ann Rheum Dis: first published as 10.1136/ard.2003.017566 on 26 August 2004. Downloaded from EXTENDED REPORT Increased expression of CCL18, CCL19, and CCL17 by dendritic cells from patients with rheumatoid arthritis, and regulation by Fc gamma receptors T R D J Radstake, R van der Voort, M ten Brummelhuis, M de Waal Malefijt, M Looman, C G Figdor, W B van den Berg, P Barrera, G J Adema ............................................................................................................................... Ann Rheum Dis 2005;64:359–367. doi: 10.1136/ard.2003.017566 See end of article for authors’ affiliations ....................... Background: Dendritic cells (DC) have a role in the regulation of immunity and tolerance, attracting Correspondence to: inflammatory cells by the production of various chemokines (CK). Fc gamma receptors (FccR) may be Dr T R D J Radstake, involved in regulation of the DC function. Department of Objective: To assess the expression of CK by immature (iDC) and mature DC (mDC) and its regulation by Rheumatology/Laboratory of Experimental FccR in patients with RA and healthy donors (HC). Rheumatology and Methods: Expression of CK by DC from patients with RA and from HC was determined by real time Advanced Therapeutics, quantitative PCR and ELISA. DC were derived from monocytes following standardised protocols. To study University Medical Centre the potential regulation by FccR, iDC were stimulated with immune complexes (IC) during Nijmegen, The Netherlands and lipopolysaccharide (LPS) induced maturation. The presence of CK was studied in synovial tissue from Nijmegen Centre for patients with RA, osteoarthritis, and healthy subjects by RT-PCR and immunohistochemistry. Molecular Life Sciences, Results: iDC from patients with RA had markedly increased mRNA levels of the CK CCL18 and CXCL8.
    [Show full text]
  • A Novel Α9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases
    A Novel α9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases This information is current as of September 25, 2021. Naoki Matsumoto, Shigeyuki Kon, Takuya Nakatsuru, Tomoe Miyashita, Kyosuke Inui, Kodai Saitoh, Yuichi Kitai, Ryuta Muromoto, Jun-ichi Kashiwakura, Toshimitsu Uede and Tadashi Matsuda J Immunol 2017; 199:82-90; Prepublished online 26 May Downloaded from 2017; doi: 10.4049/jimmunol.1601329 http://www.jimmunol.org/content/199/1/82 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2017/05/26/jimmunol.160132 Material 9.DCSupplemental References This article cites 40 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/199/1/82.full#ref-list-1 by guest on September 25, 2021 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 *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 © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology A Novel a9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases Naoki Matsumoto,*,1 Shigeyuki Kon,*,†,1 Takuya Nakatsuru,* Tomoe Miyashita,* Kyosuke Inui,* Kodai Saitoh,* Yuichi Kitai,* Ryuta Muromoto,* Jun-ichi Kashiwakura,* Toshimitsu Uede,‡ and Tadashi Matsuda* The integrin a9b1 is a key receptor involved in the development of autoimmune diseases.
    [Show full text]
  • Tumour Immunology: NK Cells Bring in the Troops
    RESEARCH HIGHLIGHTS Nature Reviews Immunology | Published online 16 Feb 2018; doi:10.1038/nri.2018.14 Macmillan Publishers Limited TUMOUR IMMUNOLOGY NK cells bring in the troops The presence of conventional type 1 dendritic Xcl1 mRNA. Intracellular flow cytometry analyses cells (cDC1s) in tumours has been associated with of cells from COX-deficient tumours four days enhanced antitumour immunity, but it has been after implantation showed that NK cells expressed higher unclear what promotes their infiltration. A recent CCL5 protein and Xcl1 mRNA, while some rare expression study from Caetano Reis e Sousa and colleagues tumour-infiltrating CD8+ T cells expressed CCL5 now shows that natural killer (NK) cells recruit but not Xcl1. of NK cell cDC1s to the tumour microenvironment by cDC1s express the CCL5 receptors CCR1 and and cDC1 producing the chemokines CCL5 and XCL1. CCR5 as well as XCR1, the receptor for XCL1, signature The same authors previously reported that and the authors showed that they migrate genes in tumours suppress cDC1-dependent CD8+ T cell towards these chemokines in transwell assays. antitumour responses by producing Moreover, antibody-mediated blockade of tumour prostaglandin E2 (PGE2), and that deletion CCL5 and XCL1 in vivo markedly reduced cDC1 samples was of the cyclooxygenase (COX) enzymes that accumulation in COX-deficient tumours. Further associated are necessary for PGE2 synthesis enhances studies revealed that PGE2 reduces NK cell survival antitumour immunity. They therefore compared within tumours and inhibits their production of with increased cDC1 accumulation in the tumours of mice that CCL5 and XCL1, as well as impairing cDC1 patient were implanted with COX-deficient BRAFV600E responsiveness to these chemokines.
    [Show full text]
  • The Role of Specific Chemokines in the Amelioration of Colitis By
    biomolecules Article The Role of Specific Chemokines in the Amelioration of Colitis by Appendicitis and Appendectomy Rajkumar Cheluvappa 1,* ID , Dennis G. Thomas 2 and Selwyn Selvendran 3 ID 1 Department of Medicine, St. George Clinical School, University of New South Wales, Sydney, NSW 2052, Australia 2 Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA; [email protected] 3 Department of Surgery, St. George Hospital, Kogarah, NSW 2217, Australia; [email protected] * Correspondence: [email protected]; Tel.: +61-0406-0406-20; Fax: +61-02-9385-1389 Received: 13 June 2018; Accepted: 16 July 2018; Published: 20 July 2018 Abstract: The appendix contains abundant lymphoid tissue and is constantly exposed to gut flora. When completed at a young age, appendicitis followed by appendectomy (AA) prevents or significantly ameliorates Inflammatory Bowel Diseases (IBDs) in later life. Inflammatory bowel disease comprises Crohn’s disease and ulcerative colitis. Our murine AA model is the only existing experimental model of AA. In our unique model, AA performed in the most proximal colon limits colitis pathology in the most distal colon by curbing T-helper 17 cell activity, diminishing autophagy, modulating interferon activity-associated molecules, and suppressing endothelin vaso-activity-mediated immunopathology. In the research presented in this paper, we have examined the role of chemokines in colitis pathology with our murine AA model. Chemokines are a family of small cytokines with four conserved cysteine residues. Chemokines induce chemotaxis in adjacent cells with corresponding receptors. All 40 known chemokine genes and 24 chemokine receptor genes were examined for gene expression levels in distal colons three days post-AA and 28 days post-AA.
    [Show full text]
  • Products for Chemokine Research
    RnDSy-lu-2945 Products for Chemokine Research The Chemokine Superfamily Chemokines are small cell surface-localized or secreted chemotactic cytokines that bind to and activate specific G protein-coupled chemokine receptors. Most chemokines have at least four conserved N-terminal cysteine residues that form two intramolecular disulfide bonds. Four chemokine subfamilies (CXC, CC, C and CX3C) have been defined based upon the placement of the first two cysteine residues. The CXC chemokine subfamily is characterized by two cysteine residues separated by one amino acid. Within this subfamily, two CXC classes are further defined by the presence or absence of an ELR motif sequence. ELR– CXC chemokines act as chemoattractants for lymphocytes, while ELR+ CXC chemokines are chemoattractants for neutrophils. Additionally, CXC chemokines can mediate angiogenesis.1 The CC chemokine subfamily is defined by two adjacent cysteine CCR1 H: CCL3-5, 7, 8, 13-16, 23, CCL3L1, CCL3L3, CCL4L1, CCL4L2 M: CCL3-7, 9/10 residues. CC chemokines induce inflammatory H: XCL1, 2 XCR1 responses via regulation of monocyte, M: XCL1 macrophage, mast cell, and T cell migration.2 H: CCL2, 7, 8, 13, 16 CCR2 (A or B) M: CCL2, 7, 12 C chemokines are characterized by a single H: CCL26 CX3CR1 cysteine residue and are constitutively expressed H: CX3CL1 in the thymus where they regulate T cell H: CCL5, 7, 8, 11, 13, 14, 15, 24, 26, 28, CCL3L1, CCL3L3 M: CX3CL1 CCR3 M: CCL5, 7, 9/10, 11, 24 differentiation.3 The CX3C chemokine subfamily is defined by two cysteine residues separated by H: CXCL6-8 CXCR1 three amino acids.
    [Show full text]