DOCSLIB.ORG

Chemokine Signatures of Pathogen-Specific T Cells II: Memory T Cells in Acute and Chronic Infection

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chemokine Signatures of Pathogen-Specific T Cells II: Memory T Cells in Acute and Chronic Infection Chemokine Signatures of Pathogen-Specific T Cells II: Memory T Cells in Acute and Chronic Infection This information is current as Bennett Davenport, Jens Eberlein, Tom T. Nguyen, of September 24, 2021. Francisco Victorino, Verena van der Heide, Maxim Kuleshov, Avi Ma'ayan, Ross Kedl and Dirk Homann J Immunol published online 18 September 2020 http://www.jimmunol.org/content/early/2020/09/17/jimmun ol.2000254 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2020/09/17/jimmunol.200025 Material 4.DCSupplemental 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 © 2020 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published September 18, 2020, doi:10.4049/jimmunol.2000254 The Journal of Immunology Chemokine Signatures of Pathogen-Specific T Cells II: Memory T Cells in Acute and Chronic Infection Bennett Davenport,*,†,‡,x,{ Jens Eberlein,*,† Tom T. Nguyen,*,‡ Francisco Victorino,*,†,‡ Verena van der Heide,x,{ Maxim Kuleshov,‖,# Avi Ma’ayan,‖,# Ross Kedl,† and Dirk Homann*,†,‡,x,{ Pathogen-specific memory T cells (TM) contribute to enhanced immune protection under conditions of reinfection, and their effective recruitment into a recall response relies, in part, on cues imparted by chemokines that coordinate their spatiotemporal positioning. An integrated perspective, however, needs to consider TM as a potentially relevant chemokine source themselves. In this study, we employed a comprehensive transcriptional/translational profiling strategy to delineate the identities, expression + patterns, and dynamic regulation of chemokines produced by murine pathogen-specific TM. CD8 TM, and to a lesser extent + Downloaded from CD4 TM, are a prodigious source for six select chemokines (CCL1/3/4/5, CCL9/10, and XCL1) that collectively constitute a + prominent and largely invariant signature across acute and chronic infections. Notably, constitutive CCL5 expression by CD8 TM serves as a unique functional imprint of prior antigenic experience; induced CCL1 production identifies highly polyfunctional + + + CD8 and CD4 TM subsets; long-term CD8 TM maintenance is associated with a pronounced increase of XCL1 production + capacity; chemokines dominate the earliest stages of the CD8 TM recall response because of expeditious synthesis/secretion kinetics (CCL3/4/5) and low activation thresholds (CCL1/3/4/5/XCL1); and TM chemokine profiles modulated by persisting viral Ags exhibit both discrete functional deficits and a notable surplus. Nevertheless, recall responses and partial virus control in http://www.jimmunol.org/ chronic infection appear little affected by the absence of major TM chemokines. Although specific contributions of TM-derived chemokines to enhanced immune protection therefore remain to be elucidated in other experimental scenarios, the ready visu- alization of TM chemokine-expression patterns permits a detailed stratification of TM functionalities that may be correlated with differentiation status, protective capacities, and potential fates. The Journal of Immunology, 2020, 205: 000–000. athogen-specific memory T cells (TM) are an integral The choreography of these events is, in part, governed by che- component of the anamnestic immune response and can mokines, a large family of mostly secreted small molecules that P provide immune protection by curtailing secondary (II˚) regulates the spatiotemporal positioning of motile cells (6–8). by guest on September 24, 2021 infections, limiting morbidity, and forestalling potential host death Pathogen-specific TM, by virtue of their distinct chemokine (1–5). These clinical outcomes are the net result of highly com- receptor expression patterns, are acutely attuned to varied che- plex and coordinated interactions between multiple organ systems, mokine cues, as demonstrated in numerous in vitro and in vivo tissues, cell types, and extracellular factors that are marshaled into studies (6–11); however, as has been known for over two decades action following pathogen detection, and the relevant contribu- (12), T cells are also a relevant source for certain chemokines tions of specific TM to these processes are grounded in three themselves, notably for CCL3, CCL4, and CCL5, which, beyond fundamental determinants: their numbers, their location, and their their chemotactic functions, can also act as competitive inhibitors differentiation status (i.e., the particular phenotypic, molecular, of HIV binding to its coreceptor CCR5 (13–15); at micromolar and epigenetic makeup that permits TM populations to respond concentrations, CCL5 may exert receptor-independent cellular with the elaboration of rapid effector activities as well as coop- activation, apoptosis, and even antimicrobial activity, although erative cellular interactions, local and systemic mobilization, II˚ some of the evidence is contradictory and the in vivo relevance effector T cell [TE] differentiation, and proliferative expansion). unclear (16–21). Several other chemokines, including CCL1, *Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz JDRF Grant CDA 2-2007-240 (to D.H.). The funders had no role in study design, Medical Campus, Aurora, CO 80045; †Department of Immunology and Microbiol- data collection and analysis, decision to publish, or preparation of the manuscript. ogy, University of Colorado Anschutz Medical Campus, Aurora, CO 80045; The microarray data presented in this article have been submitted to Gene Expression ‡Department of Anesthesiology, University of Colorado Anschutz Medical Campus, x Omnibus (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE143632. Aurora, CO 80045; Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; {Precision Immunology Institute, Address correspondence and reprint requests to Prof. Dirk Homann, Diabetes, Icahn School of Medicine at Mount Sinai, New York, NY; ‖Department of Pharma- Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, cological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; One Gustave L. Levy Place, Box 1152, New York, NY 10029. E-mail address: and #Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount [email protected] Sinai, New York, NY 10029 The online version of this article contains supplemental material. ORCIDs: 0000-0002-6268-1767 (J.E.); 0000-0003-4222-4099 (T.T.N.); 0000-0002- + Abbreviations used in this article: Arm, Armstrong; BFA, brefeldin A; CD8 TMP, 3602-4405 (V.v.d.H.); 0000-0002-7812-7752 (M.K.); 0000-0002-7622-5754 (D.H.). + memory-phenotype CD8 T cell; CHX, cycloheximide; cl13, clone 13; ET50, 50% Received for publication March 9, 2020. Accepted for publication August 7, 2020. effective time; FC, flow cytometry; FRC, fibroblastic reticular cell; Gzm, granzyme; I˚, primary; II˚, secondary; LCMV, lymphocytic choriomeningitis virus; MHC-I, This work was supported by National Institutes of Health (NIH) Grants AG026518 MHC class I; rLM-OVA, recombinant Listeria monocytogenes expressing full- and AI093637, a Barbara Davis Center Pilot and Feasibility grant, NIH/Diabetes length OVA; T , central T ;T, effector T cell; T , effector T ;T , memory Endocrinology Research Center Grant P30-DK057516 (to D.H.), NIH Grants U54- CM M E EM M M T cell. HL127624 and U24-CA224260 (to A.M.), and NIH Training Grants T32 AI07405, T32 AI052066, and T32 DK007792 (to B.D.). This work was also supported by Copyright Ó 2020 by The American Association of Immunologists, Inc. 0022-1767/20/$37.50 www.jimmunol.org/cgi/doi/10.4049/jimmunol.2000254 2 CHEMOKINE SIGNATURES OF PATHOGEN-SPECIFIC MEMORY T CELLS CCL9/10, and XCL1, have further been reported as products of (IACUC-2014-0170), and all efforts were made to minimize suffering of animals. pathogen-specific TM (22–26), but to date, experimental evidence in support of pathogen-specific, TM-derived chemokines as non- Mice, pathogens, and challenge/vaccination protocols redundant contributors to effective immune protection at the level C57BL6/J (B6), congenic B6.CD90.1 (B6.PL-Thy1a/CyJ), congenic B6.CD45.1 of II˚ T expansion, pathogen control, and/or host survival re- a b 2/2 tm1Unc/ E (B6.SJL-Ptprc Pepc /BoyJ), and B6.CCL3 (B6.129P2-Ccl3 J) mains limited to CCL3 and possibly XCL1 in some, but not other, mice on a B6 background as well as BALB/c mice were purchased murine model systems (27, 28). from The Jackson Laboratory; p14 TCR transgenic mice were obtained + Chemokine synthesis and secretion by TM, similar to other on a B6.CD90.1 background from Dr. M. Oldstone (CD8 T cells from effector functions, such as cytokine and TNFSF ligand pro- these mice [p14 cells] are specific for the dominant lymphocytic choriomeningitis virus [LCMV]-GP33–41 determinant restricted by duction, typically
Load more

Recommended publications
  • Mouse CD163 Deficiency Strongly Enhances Experimental Collagen-Induced Arthritis
    www.nature.com/scientificreports OPEN Mouse CD163 defciency strongly enhances experimental collagen‑induced arthritis Pia Svendsen1,2, Anders Etzerodt 3, Bent W. Deleuran3,4 & Søren K. Moestrup1,2,5* The scavenger receptor CD163 is highly expressed in macrophages in sites of chronic infammation where it has a not yet defned role. Here we have investigated development of collagen‑induced arthritis (CIA) and collagen antibody‑induced arthritis (CAIA) in CD163‑defcient C57BL/6 mice. Compared to wild‑type mice, the CIA in CD163‑defcient mice had a several‑fold higher arthritis score with early onset, prolonged disease and strongly enhanced progression. Further, the serum anti‑ collagen antibody isotypes as well as the cytokine profles and T cell markers in the infamed joints revealed that CD163‑defcient mice after 52 days had a predominant Th2 response in opposition to a predominant Th1 response in CD163+/+ mice. Less diference in disease severity between the CD163+/+ and CD163−/− mice was seen in the CAIA model that to a large extent induces arthritis independently of T‑cell response and endogenous Th1/Th2 balance. In conclusion, the present set of data points on a novel strong anti‑infammatory role of CD163. Te scavenger receptor CD163 is expressed exclusively in cells of monocytic origin with a high expression in M2-type macrophages where it has an established role in scavenging hemoglobin (Hb) released into plasma 1. Te receptor and its function have been most intensively studied in human systems, but the selective myelomonocytic expression of CD163 with a high upregulation in the M2-type macrophages is also seen in animals including rodents2,3.
    [Show full text]
  • Differentiation and Bone Resorption Role of CX3CL1/Fractalkine In
    Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption Keiichi Koizumi, Yurika Saitoh, Takayuki Minami, Nobuhiro Takeno, Koichi Tsuneyama, Tatsuro Miyahara, This information is current as Takashi Nakayama, Hiroaki Sakurai, Yasuo Takano, Miyuki of September 29, 2021. Nishimura, Toshio Imai, Osamu Yoshie and Ikuo Saiki J Immunol published online 18 November 2009 http://www.jimmunol.org/content/early/2009/11/18/jimmuno l.0803627.citation 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 29, 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 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published November 18, 2009, doi:10.4049/jimmunol.0803627 The Journal of Immunology Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption1 Keiichi Koizumi,2* Yurika Saitoh,* Takayuki Minami,* Nobuhiro Takeno,* Koichi Tsuneyama,†‡ Tatsuro Miyahara,§ Takashi Nakayama,¶ Hiroaki Sakurai,*† Yasuo Takano,‡ Miyuki Nishimura,ʈ Toshio Imai,ʈ Osamu Yoshie,¶ and Ikuo Saiki*† The recruitment of osteoclast precursors toward osteoblasts and subsequent cell-cell interactions are critical for osteoclast dif- ferentiation.
    [Show full text]
  • Complementary DNA Microarray Analysis of Chemokines and Their Receptors in Allergic Rhinitis RX Zhang,1 SQ Yu,2 JZ Jiang,3 GJ Liu3
    RX Zhang, et al ORIGINAL ARTICLE Complementary DNA Microarray Analysis of Chemokines and Their Receptors in Allergic Rhinitis RX Zhang,1 SQ Yu,2 JZ Jiang,3 GJ Liu3 1 Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai, China 2 Department of Otolaryngology , Jinan General Hospital of PLA, Shandong, China 3 Department of Otolaryngology, Changhai Hospital, Second Military Medical University, Shanghai, China ■ Abstract Objective: To analyze the roles of chemokines and their receptors in the pathogenesis of allergic rhinitis by observing the complementary DNA (cDNA) expression of the chemokines and their receptors in the nasal mucosa of patients with and without allergic rhinitis, using gene chips. Methods: The total RNAs were isolated from the nasal mucosa of 20 allergic rhinitis patients and purifi ed to messenger RNAs, and then reversely transcribed to cDNAs and incorporated with samples of fl uorescence-labeled with Cy5-dUPT (rhinitis patient samples) or Cy3- dUTP (control samples of nonallergic nasal mucosa). Thirty-nine cDNAs of chemokines and their receptors were latticed into expression profi le chips, which were hybridized with probes and then scanned with the computer to study gene expression according to the different fl uorescence intensities. Results: The cDNAs of the following chemokines were upregulated: CCL1, CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL14, CCL17, CCL18, CCL19, CCL24, and CX3CL1 in most of the allergic rhinitis sample chips. CCR2, CCR3, CCR4, CCR5, CCR8 and CX3CR1 were the highly expressed receptor genes. Low expression of CXCL4 was found in these tissues. Conclusion: The T helper cell (TH) immune system is not well regulated in allergic rhinitis.
    [Show full text]
  • Ccl9 Induced by Tgf-Β Signaling in Myeloid Cells Enhances Tumor Cell Survival in the Premetastatic Lung
    CCL9 INDUCED BY TGF-β SIGNALING IN MYELOID CELLS ENHANCES TUMOR CELL SURVIVAL IN THE PREMETASTATIC LUNG by Hangyi Yan A dissertation submitted to Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland March, 2015 ABSTRACT The majority of cancer patients die from metastasis. To achieve metastasis, tumor cells must first survive and then proliferate to form colonies. Compelling data have shown the indispensable participation of host microenvironment for metastasis. Bone marrow derived myeloid cells sculpt a tumor-promoting microenvironment in the premetastatic organs prior to tumor cell arrival. However, the molecular mechanisms for this “seed and soil” hypothesis are unclear. Here we report that CCL9 was significantly produced and secreted by Gr-1+CD11b+ cells when co-cultured with tumor cells, and in the premetastatic lung. CCL9 knockdown (KD) in myeloid cells decreased metastasis, and this process signaled through its sole receptor CCR1. Overexpression of CCR1 lost the metastasis-promoting function in the context of CCL9 KD. CCL9 enhanced tumor cell survival in the premetastatic organs. The underlying molecular mechanisms included activation of cell survival factors phosphorylated AKT and BCL-2, as well as inhibition of Poly (ADP-ribose) polymerase (PARP)-dependent apoptosis pathway. Additionally, CCL9/CCR1 had autocrine effects, which enhanced CCL9 secretion and the survival of Gr-1+CD11b+ cells. We found that CCL9 was a key effector of myeloid transforming growth factor β (TGF-β) pathway that promotes metastasis. Decreased metastasis in mice with myeloid specific TGF-β receptor II deletion (Tgfbr2MyeKO) correlated with lower CCL9 expression in TGF-β deficient myeloid cells.
    [Show full text]
  • Bioinformatics Identification of CCL8/21 As Potential Prognostic
    Bioscience Reports (2020) 40 BSR20202042 https://doi.org/10.1042/BSR20202042 Research Article Bioinformatics identification of CCL8/21 as potential prognostic biomarkers in breast cancer microenvironment 1,* 2,* 3 4 5 1 Bowen Chen , Shuyuan Zhang ,QiuyuLi, Shiting Wu ,HanHe and Jinbo Huang Downloaded from http://portlandpress.com/bioscirep/article-pdf/40/11/BSR20202042/897847/bsr-2020-2042.pdf by guest on 28 September 2021 1Department of Breast Disease, Maoming People’s Hospital, Maoming 525000, China; 2Department of Clinical Laboratory, Maoming People’s Hospital, Maoming 525000, China; 3Department of Emergency, Maoming People’s Hospital, Maoming 525000, China; 4Department of Oncology, Maoming People’s Hospital, Maoming 525000, China; 5Department of Medical Imaging, Maoming People’s Hospital, Maoming 525000, China Correspondence: Shuyuan Zhang ([email protected]) Background: Breast cancer (BC) is the most common malignancy among females world- wide. The tumor microenvironment usually prevents effective lymphocyte activation and infiltration, and suppresses infiltrating effector cells, leading to a failure of the host toreject the tumor. CC chemokines play a significant role in inflammation and infection. Methods: In our study, we analyzed the expression and survival data of CC chemokines in patients with BC using several bioinformatics analyses tools. Results: The mRNA expression of CCL2/3/4/5/7/8/11/17/19/20/22 was remark- ably increased while CCL14/21/23/28 was significantly down-regulated in BC tis- sues compared with normal tissues. Methylation could down-regulate expression of CCL2/5/15/17/19/20/22/23/24/25/26/27 in BC. Low expression of CCL3/4/23 was found to be associated with drug resistance in BC.
    [Show full text]
  • US7572600.Pdf
    US007572600B2 (12) United States Patent (10) Patent No.: US 7,572,600 B2 Berahovich et al. (45) Date of Patent: Aug. 11, 2009 (54) ENZYMATIC ACTIVITIES IN WO WO90, 13332 11, 1990 CHEMOKNE-MEDIATED INFLAMMATION WO WO 91/12779 9, 1991 WO WO 91f17271 11, 1991 (75) WO WO91, 1898O 12/1991 Inventors: Robert D. Berahovich, Berkeley, CA WO WO92fO1047 1, 1992 (US); Zhenhua Miao, San Jose, CA WO WO93,06121 4f1993 (US); Brett Premack, San Francisco, WO WO93, 17706 9, 1993 CA (US); Thomas J. Schall, Palo Alto, WO WO93/24640 12/1993 CA (US) WO WO94,08051 4f1994 WO WO94/20142 9, 1994 (73) Assignee: Chemocentryx, Inc., Mt. View, CA (US) WO WO95/12608 5, 1995 WO WO95/30642 11, 1995 (*) Notice: Subject to any disclaimer, the term of this WO WO95/35503 12/1995 patent is extended or adjusted under 35 WO WO 98.04554 2, 1998 U.S.C. 154(b) by 486 days. OTHER PUBLICATIONS (21) Appl. No.: 11/198,935 Al-Obeidi (1998), Mol. Biotechnol. 9:205-223. Aoyama, Y. et al. (2001), Bioorg Med. Chem. Lett. 11: 1691-4. (22) Filed: Aug. 4, 2005 Amour, A., et al. (1998), J. Pharm. Pharmacol. 50:593-600. Berger, M.S. etal (1993), DNA Cell Biol 12:839-847. (65) Prior Publication Data Bao, L., et al. (1992), Genomics 13:437-40. US 2006/OO63223 A1 Mar. 23, 2006 Berman et al. (1988), Immunol. Invest. 17: 625-677. Baici, A. (1993), Biochem. Pharmacol. 46:1545-9. Bae, Y.-S. et al. (2004) J Immunol. 173:607-614.
    [Show full text]
  • Metastasis: Active Lymph Nodes
    RESEARCH HIGHLIGHTS METASTASIS subcapsular sinus. Further investiga- tions in vivo revealed that CCR8 acti- vation in tumour cells was required Active lymph nodes for tumour cell extravasation from lymphatic vessels, specifically for the Lymph node metastases are CCL1 activates CCR8-mediated transmigration of tumour cells from indicative of poor prognosis but intracellular signalling in tumour the subcapsular sinus into the lymph tumour cell the mechanisms of tumour cell cells, which resulted in cellular node cortex. entry into the dissemination via the lymphatics changes that are consistent with cell These data unpick the process of are poorly understood. Although it migration. lymphatic dissemination and iden- lymph node is widely believed that tumour cells Is the CCR8–CCL1 paracrine tify the sequence of steps leading to requires active enter the lymph nodes passively with pathway important in lymphatic lymph node metastasis. The authors cell migration the flow of lymph, previous data have metastasis? The suppression of showed that CCR8 is expressed by indicated that some chemokines may CCR8 expression or activity in a large subset of human melanoma promote lymphatic extravasation human melanoma cells did not samples, and it will be interesting and metastasis. Das et al. now dem- affect tumour growth or vasculariz­ to determine whether this pathway onstrate that tumour cell entry into ation on implantation into immuno­ can be targeted to prevent lymph the lymph node requires active cell deficient mice, but significantly node metastasis. migration and they also identify the reduced the incidence of lymph Gemma K. Alderton lymphatic endothelium of the lymph node metastasis. Furthermore, ORIGINAL RESEARCH PAPER Das, S.
    [Show full text]
  • Responses During Sepsis Interactions Exacerbate Innate Immune CCR1
    The Journal of Immunology CCR1 and CC Chemokine Ligand 5 Interactions Exacerbate Innate Immune Responses during Sepsis1 Traci L. Ness,* Kristin J. Carpenter,* Jillian L. Ewing,* Craig J. Gerard,† Cory M. Hogaboam,2* and Steven L. Kunkel* CCR1 has previously been shown to play important roles in leukocyte trafficking, pathogen clearance, and the type 1/type 2 cytokine balance, although very little is known about its role in the host response during sepsis. In a cecal ligation and puncture model of septic peritonitis, CCR1-deficient (CCR1؊/؊) mice were significantly protected from the lethal effects of sepsis when compared with wild-type (WT) controls. The peritoneal and systemic cytokine profile in CCR1؊/؊ mice was characterized by a robust, but short-lived and regulated antibacterial response. CCR1 expression was not required for leu- -kocyte recruitment, suggesting critical differences extant in the activation of WT and CCR1؊/؊ resident or recruited peri toneal cells during sepsis. Peritoneal macrophages isolated from naive CCR1؊/؊ mice clearly demonstrated enhanced cytokine/chemokine generation and antibacterial responses compared with similarly treated WT macrophages. CCR1 and CCL5 interactions markedly altered the inflammatory response in vivo and in vitro. Administration of CCL5 increased sepsis-induced lethality in WT mice, whereas neutralization of CCL5 improved survival. CCL5 acted in a CCR1-dependent manner to augment production of IFN-␥ and MIP-2 to damaging levels. These data illustrate that the interaction between CCR1 and CCL5 modulates the innate immune response during sepsis, and both represent potential targets for therapeutic intervention. The Journal of Immunology, 2004, 173: 6938–6948. epsis is the most common cause of death in noncoronary mune response to sepsis (7, 8).
    [Show full text]
  • Retinoid X Receptor Α Controls Innate Inflammatory Responses Through The
    Retinoid X receptor α controls innate inflammatory responses through the up-regulation of chemokine expression Vanessa Núñeza,1, Daniel Alamedaa,1, Daniel Ricoa,2, Rubén Motab, Pilar Gonzalob, Marta Cedenillaa, Thierry Fischerc, Lisardo Boscád, Christopher K. Glasse, Alicia G. Arroyob, and Mercedes Ricotea,3 Departments of aRegenerative Cardiology and bVascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain; cDepartment of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid 28049, Spain; dInstituto de Investigaciones Biomédicas “Alberto Sols” (CSIC-UAM), Madrid 28029, Spain; and eDepartment of Medicine, Department of Cellular and Molecular Medicine, University of California, La Jolla, CA 92093 Edited* by Daniel Steinberg, University of California, La Jolla, CA, and approved April 19, 2010 (received for review November 25, 2009) The retinoid X receptor α (RXRα) plays a central role in the regulation Chemokines and their receptors have been implicated in the of many intracellular receptor signaling pathways and can mediate modulation of leukocyte trafficking, immune/inflammatory respon- ligand-dependent transcription by forming homodimers or hetero- ses, sepsis, and multiorgan failure (18, 19). Clinical studies have also dimers with other nuclear receptors. Although several members of identified elevated levels of chemokines associated with human the nuclear hormone receptor superfamily have emerged as impor- sepsis and acute lung injury (20). tant regulators of macrophage gene expression, the existence in vivo We have examined the role of RXRα in the innate immune of an RXR signaling pathway in macrophages has not been estab- system by conditionally disrupting RXRα in myeloid cells. We lished. Here, we provide evidence that RXRα regulates the transcrip- show that chemokines Ccl6 and Ccl9 are novel target genes for tion of the chemokines Ccl6 and Ccl9 in macrophages independently RXRα in primary peritoneal macrophages.
    [Show full text]
  • CCL9 Is Secreted by the Follicle-Associated Epithelium and Recruits Dome Region Peyer's Patch Cd11b+ Dendritic Cells
    CCL9 Is Secreted by the Follicle-Associated Epithelium and Recruits Dome Region Peyer's Patch CD11b+ Dendritic Cells This information is current as Xinyan Zhao, Ayuko Sato, Charles S. Dela Cruz, Melissa of October 1, 2021. Linehan, Andreas Luegering, Torsten Kucharzik, Aiko-Konno Shirakawa, Gabriel Marquez, Joshua M. Farber, Ifor Williams and Akiko Iwasaki J Immunol 2003; 171:2797-2803; ; doi: 10.4049/jimmunol.171.6.2797 http://www.jimmunol.org/content/171/6/2797 Downloaded from References This article cites 32 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/171/6/2797.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 October 1, 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 Errata An erratum has been published regarding this article. Please see next page or: /content/172/11/7220.2.full.pdf 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 © 2003 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology CCL9 Is Secreted by the Follicle-Associated Epithelium and Recruits Dome Region Peyer’s Patch CD11b؉ Dendritic Cells1 Xinyan Zhao,2* Ayuko Sato,* Charles S.
    [Show full text]
  • Myelin-Specific CD8 T Cells Exacerbate Brain Inflammation in CNS Autoimmunity
    Myelin-specific CD8 T cells exacerbate brain inflammation in CNS autoimmunity Catriona A. Wagner, … , Denny Liggitt, Joan M. Goverman J Clin Invest. 2019. https://doi.org/10.1172/JCI132531. Research In-Press Preview Autoimmunity Graphical abstract Find the latest version: https://jci.me/132531/pdf Myelin-specific CD8 T cells exacerbate brain inflammation in CNS autoimmunity Catriona A. Wagner1, Pamela J. Roqué1, Trevor R. Mileur1, Denny Liggitt2, and Joan M. Goverman1* 1Departments of Immunology and 2Comparative Medicine, University of Washington, Seattle, WA, USA *Corresponding author: Dr. Joan M. Goverman Department of Immunology, University of Washington Box 358059 750 Republican St, Seattle, WA 98109 Tel: +1 206-685-7604 Fax: +1 206-616-4561 Email: [email protected] The authors declare no competing financial interests. Abstract Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS. Although CD4 T cells are implicated in MS pathogenesis and have been the main focus of MS research using the animal model experimental autoimmune encephalomyelitis (EAE), substantial evidence from patients with MS points to a role for CD8 T cells in disease pathogenesis. We previously showed that an MHC class I-restricted epitope of myelin basic protein (MBP) is presented in the CNS during CD4 T cell-initiated EAE. Here, we investigated whether naïve MBP-specific CD8 T cells recruited to the CNS during CD4 T cell-initiated EAE engaged in determinant-spreading and influenced disease. We found that the MBP-specific CD8 T cells exacerbated brain but not spinal cord inflammation. We show that a higher frequency of monocytes and monocyte-derived cells presented the MHC class I-restricted MBP ligand in the brain compared to the spinal cord.
    [Show full text]
  • Identification of CCL1 As a Gene Differentially Expressed in CD4＋ T Cells Expressing TIM-3
    http://dx.doi.org/10.4110/in.2011.11.4.203 ORIGINAL ARTICLE pISSN 1598-2629 eISSN 2092-6685 Identification of CCL1 as a Gene Differentially Expressed in CD4＋ T cells Expressing TIM-3 Ka Jung Jun1,2, Mi Jin Lee1,2, Dong Chul Shin1,2, Min Yeong Woo1,2, Kyongmin Kim1 and Sun Park1* 1Department of Microbiology and 2Graduate Program of Molecular Medicine, Ajou University School of Medicine, Suwon 442-749, Korea Background: T cell immunoglobulin mucin containing mole- responses and the pathogenesis of several diseases (1). With cule (TIM)-3 is expressed in differentiated Th1 cells and is in- its blocking antibody or its soluble fusion protein TIM-3-Ig, volved in the suppression of the cytokine production by these Th1 immune response as well as anti-tumor immunity is en- cells. However, the regulation of the expression of other T hanced (2-4). Also, induction of tolerance in an experimental cell genes by TIM-3 is unclear. Herein, we attempted to iden- transplantation model is abrogated by injection of TIM-3 anti- tify differentially expressed genes in cells abundantly ex- body (5). Furthermore, dysregulation of T cell TIM-3 ex- pressing TIM-3 compared to cells with low expression of pression is observed in several autoimmune diseases includ- TIM-3. Methods: TIM-3 overexpressing cell clones were es- ing multiple sclerosis, rheumatoid arthritis and Crohn s dis- tablished by transfection of Jurkat T cells with TIM-3 ex- ’ pression vector. For screening of differentially expressed ease (6-8). genes, gene fishing technology based on reverse tran- Galectin-9 and phosphatidylserine have been identified as scription-polymerase chain reaction (RT-PCR) using an an- TIM-3 ligands.
    [Show full text]