For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
55
views
132
references
 Top references
cited by
45
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      525
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      The CXCL10/CXCR3 Axis and Cardiac Inflammation: Implications for Immunotherapy to Treat Infectious and Noninfectious Diseases of the Heart

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Accumulating evidence reveals involvement of T lymphocytes and adaptive immunity in the chronic inflammation associated with infectious and noninfectious diseases of the heart, including coronary artery disease, Kawasaki disease, myocarditis, dilated cardiomyopathies, Chagas, hypertensive left ventricular (LV) hypertrophy, and nonischemic heart failure. Chemokine CXCL10 is elevated in cardiovascular diseases, along with increased cardiac infiltration of proinflammatory Th1 and cytotoxic T cells. CXCL10 is a chemoattractant for these T cells and polarizing factor for the proinflammatory phenotype. Thus, targeting the CXCL10 receptor CXCR3 is a promising therapeutic approach to treating cardiac inflammation. Due to biased signaling CXCR3 also couples to anti-inflammatory signaling and immunosuppressive regulatory T cell formation when activated by CXCL11. Numbers and functionality of regulatory T cells are reduced in patients with cardiac inflammation, supporting the utility of biased agonists or biologicals to simultaneously block the pro-inflammatory and activate the anti-inflammatory actions of CXCR3. Other immunotherapy strategies to boost regulatory T cell actions include intravenous immunoglobulin (IVIG) therapy, adoptive transfer, immunoadsorption, and low-dose interleukin-2/interleukin-2 antibody complexes. Pharmacological approaches include sphingosine 1-phosphate receptor 1 agonists and vitamin D supplementation. A combined strategy of switching CXCR3 signaling from pro- to anti-inflammatory and improving Treg functionality is predicted to synergistically lessen adverse cardiac remodeling.

          Related collections

          Most cited references132

          • Record: found
          • Abstract: found
          • Article: not found

          Pathophysiology of coronary artery disease.

          Peter Libby, Pierre Théroux (2005)
          During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the "fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.
          Article 0 comments Cited 380 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Interleukin-2 and regulatory T cells in graft-versus-host disease.

            John Koreth, Ken-ichi Matsuoka, Haesook T. Kim … (2011)
            Dysfunction of regulatory T (Treg) cells has been detected in diverse inflammatory disorders, including chronic graft-versus-host disease (GVHD). Interleukin-2 is critical for Treg cell growth, survival, and activity. We hypothesized that low-dose interleukin-2 could preferentially enhance Treg cells in vivo and suppress clinical manifestations of chronic GVHD. In this observational cohort study, patients with chronic GVHD that was refractory to glucocorticoid therapy received daily low-dose subcutaneous interleukin-2 (0.3×10(6), 1×10(6), or 3×10(6) IU per square meter of body-surface area) for 8 weeks. The end points were safety and clinical and immunologic response. After a 4-week hiatus, patients with a response could receive interleukin-2 for an extended period. A total of 29 patients were enrolled. None had progression of chronic GVHD or relapse of a hematologic cancer. The maximum tolerated dose of interleukin-2 was 1×10(6) IU per square meter. The highest dose level induced unacceptable constitutional symptoms. Of the 23 patients who could be evaluated for response, 12 had major responses involving multiple sites. The numbers of CD4+ Treg cells were preferentially increased in all patients, with a peak median value, at 4 weeks, that was more than eight times the baseline value (P<0.001), without affecting CD4+ conventional T (Tcon) cells. The Treg:Tcon ratio increased to a median of more than five times the baseline value (P<0.001). The Treg cell count and Treg:Tcon ratio remained elevated at 8 weeks (P<0.001 for both comparisons with baseline values), then declined when the patients were not receiving interleukin-2. The increased numbers of Treg cells expressed the transcription factor forkhead box P3 (FOXP3) and could inhibit autologous Tcon cells. Immunologic and clinical responses were sustained in patients who received interleukin-2 for an extended period, permitting the glucocorticoid dose to be tapered by a mean of 60% (range, 25 to 100). Daily low-dose interleukin-2 was safely administered in patients with active chronic GVHD that was refractory to glucocorticoid therapy. Administration was associated with preferential, sustained Treg cell expansion in vivo and amelioration of the manifestations of chronic GVHD in a substantial proportion of patients. (Funded by a Dana-Farber Dunkin' Donuts Rising Star award and others; ClinicalTrials.gov number, NCT00529035.).
            Article 0 comments Cited 376 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Kawasaki Disease.

              Jane W Newburger, Masato Takahashi, Jane C. Burns (2016)
              Kawasaki disease is an acute, self-limited vasculitis of unknown etiology that occurs predominantly in infants and children. If not treated early with high-dose intravenous immunoglobulin, 1 in 5 children develop coronary artery aneurysms; this risk is reduced 5-fold if intravenous immunoglobulin is administered within 10 days of fever onset. Coronary artery aneurysms evolve dynamically over time, usually reaching a peak dimension by 6 weeks after illness onset. Almost all the morbidity and mortality occur in patients with giant aneurysms. Risk of myocardial infarction from coronary artery thrombosis is greatest in the first 2 years after illness onset. However, stenosis and occlusion progress over years. Indeed, Kawasaki disease is no longer a rare cause of acute coronary syndrome presenting in young adults. Both coronary artery bypass surgery and percutaneous intervention have been used to treat Kawasaki disease patients who develop myocardial ischemia as a consequence of coronary artery aneurysms and stenosis.
              Article 0 comments Cited 202 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): J Immunol Res
                Journal ID (iso-abbrev): J Immunol Res
                Journal ID (publisher-id): JIR
                Title: Journal of Immunology Research
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2314-8861
                ISSN (Electronic): 2314-7156
                Publication date (Print): 2016
                Publication date (Electronic): 3 October 2016
                Volume: 2016
                Electronic Location Identifier: 4396368
                Affiliations
                1Department of Pharmacology and Toxicology, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216-4500, USA
                2Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge CB20 SZ, UK
                3Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 970, Paris Cardiovascular Research Center, 75015 Paris, France
                4Department of Pharmacology and Toxicology, American University of Beirut, Faculty of Medicine, Beirut 1107 2020, Lebanon
                Author notes
                *Raffaele Altara: raltara@ 123456umc.edu

                Academic Editor: Giuseppe A. Sautto

                Author information
                http://orcid.org/0000-0001-5590-6529
                Article
                DOI: 10.1155/2016/4396368
                PMC ID: 5066021
                PubMed ID: 27795961
                SO-VID: fe137ea5-7434-4260-b783-9b05046dda93
                Copyright © Copyright © 2016 Raffaele Altara et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 17 June 2016
                Date revision received : 16 August 2016
                Date accepted : 30 August 2016
                Funding
                Funded by: Department of Pharmacology and Toxicology of the University of Mississippi Medical Center
                Award ID: 100410
                Funded by: American University of Beirut
                Funded by: European Research Council and the British Heart Foundation
                Categories
                Subject: Review Article

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content525

                See all similar

                Cited by45

                See all cited by

                Most referenced authors2,948

                See all reference authors