Special Issue "Mechanism of Action and Applications of Cytokines in Immunotherapy"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 June 2015)

Special Issue Editor

Guest Editor
Prof. Dr. Kamal D. Moudgil
Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380 Baltimore, MD 21201, USA
Website: http://medschool.umaryland.edu/FACULTYRESEARCHPROFILE/viewprofile.aspx?id=5647
Interests: autoimmunity; arthritis; immune regulation; cytokines; antigen processing and presentation; natural products; targeted therapy

Special Issue Information

Dear Colleagues,

Cytokines can be produced by a wide variety of cell types, including lymphocytes, myeloid cells, endothelial cells, and epithelial cells (under appropriate stimuli). Cytokines mediate diverse cellular, biochemical, and molecular responses in health, as well as during infection and other pathophysiological situations, including tumors and autoimmune diseases. Certain cytokines induce inflammation and tissue damage, whereas others attempt to suppress inflammation and facilitate tissue repair or recovery. Accordingly, cytokines have been broadly categorized as either pro-inflammatory or anti-inflammatory in nature. In regard to the cellular sources of such cytokines, for example, the T helper 17 (Th17) cells that produce IL-17 are involved in the pathogenesis of many autoimmune diseases, whereas the T regulatory (Treg) cells that produce IL-10 and TGF-β regulate pathogenic responses. Furthermore, different cytokines may reveal cooperative or antagonistic attributes in the course of immune dysregulation, cell death, and other pathological events. In the past decade or so, many new cytokines and effector/regulatory lymphocyte subsets have been unveiled. Also described are new subsets of macrophages and other myeloid cells. These advances have prompted an enthusiastic search for the mechanisms of action of newly discovered cytokines and their inter-relationships with previously well-known (older) cytokines. The emerging information, in turn, has stimulated the development of novel cytokine-based strategies for therapeutic purposes. For example, a spectrum of biologics is either in use or under development for the treatment of various autoimmune diseases. Similarly, strategies for the modulation of cellular/cytokine activity, so as to enhance anti-tumor immunity, are being developed. This Special Issue discusses the mechanisms of action and applications of cytokines for immunotherapeutic purposes.

Prof. Dr. Kamal D. Moudgil
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF.

Keywords

  • arthritis
  • autoimmunity
  • biologics
  • cancer
  • cytokines
  • immunotherapy
  • infection
  • interferons
  • lupus
  • lymphokines
  • multiple sclerosis
  • rheumatoid arthritis
  • tumors
  • virus

Published Papers (20 papers)

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Displaying article 1-20
p. 20841-20858
by , , , ,  and
Int. J. Mol. Sci. 2015, 16(9), 20841-20858; doi:10.3390/ijms160920841
Received: 19 June 2015 / Revised: 19 August 2015 / Accepted: 25 August 2015 / Published: 1 September 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 20100-20117
by , ,  and
Int. J. Mol. Sci. 2015, 16(9), 20100-20117; doi:10.3390/ijms160920100
Received: 27 April 2015 / Revised: 12 June 2015 / Accepted: 6 August 2015 / Published: 25 August 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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p. 18778-18795
by , ,  and
Int. J. Mol. Sci. 2015, 16(8), 18778-18795; doi:10.3390/ijms160818778
Received: 29 June 2015 / Revised: 3 August 2015 / Accepted: 6 August 2015 / Published: 11 August 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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p. 18683-18713
by  and
Int. J. Mol. Sci. 2015, 16(8), 18683-18713; doi:10.3390/ijms160818683
Received: 16 June 2015 / Revised: 13 July 2015 / Accepted: 15 July 2015 / Published: 11 August 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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p. 16622-16641
by , , , , ,  and
Int. J. Mol. Sci. 2015, 16(7), 16622-16641; doi:10.3390/ijms160716622
Received: 17 April 2015 / Revised: 5 July 2015 / Accepted: 14 July 2015 / Published: 22 July 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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p. 12958-12985
by ,  and
Int. J. Mol. Sci. 2015, 16(6), 12958-12985; doi:10.3390/ijms160612958
Received: 7 December 2014 / Revised: 3 May 2015 / Accepted: 8 May 2015 / Published: 8 June 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 10267-10280
by , ,  and
Int. J. Mol. Sci. 2015, 16(5), 10267-10280; doi:10.3390/ijms160510267
Received: 12 March 2015 / Revised: 16 April 2015 / Accepted: 29 April 2015 / Published: 6 May 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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p. 9896-9909
by , , , ,  and
Int. J. Mol. Sci. 2015, 16(5), 9896-9909; doi:10.3390/ijms16059896
Received: 7 March 2015 / Revised: 23 April 2015 / Accepted: 24 April 2015 / Published: 30 April 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 8744-8760
by , ,  and
Int. J. Mol. Sci. 2015, 16(4), 8744-8760; doi:10.3390/ijms16048744
Received: 9 March 2015 / Revised: 11 April 2015 / Accepted: 14 April 2015 / Published: 20 April 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 5497-5509
by , , ,  and
Int. J. Mol. Sci. 2015, 16(3), 5497-5509; doi:10.3390/ijms16035497
Received: 16 November 2014 / Revised: 19 February 2015 / Accepted: 27 February 2015 / Published: 10 March 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 4850-4864
by , , , , ,  and
Int. J. Mol. Sci. 2015, 16(3), 4850-4864; doi:10.3390/ijms16034850
Received: 16 November 2014 / Revised: 19 February 2015 / Accepted: 24 February 2015 / Published: 3 March 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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p. 2851-2863
by , ,  and
Int. J. Mol. Sci. 2015, 16(2), 2851-2863; doi:10.3390/ijms16022851
Received: 27 December 2014 / Revised: 19 January 2015 / Accepted: 22 January 2015 / Published: 27 January 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 1691-1710
by , , , , ,  and
Int. J. Mol. Sci. 2015, 16(1), 1691-1710; doi:10.3390/ijms16011691
Received: 15 November 2014 / Accepted: 5 January 2015 / Published: 13 January 2015
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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p. 887-906
by , ,  and
Int. J. Mol. Sci. 2015, 16(1), 887-906; doi:10.3390/ijms16010887
Received: 10 November 2014 / Accepted: 25 December 2014 / Published: 31 December 2014
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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p. 18574-18592
by
Int. J. Mol. Sci. 2014, 15(10), 18574-18592; doi:10.3390/ijms151018574
Received: 22 August 2014 / Revised: 22 September 2014 / Accepted: 8 October 2014 / Published: 15 October 2014
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 17270-17283
by , , , , ,  and
Int. J. Mol. Sci. 2014, 15(10), 17270-17283; doi:10.3390/ijms151017270
Received: 29 July 2014 / Revised: 11 September 2014 / Accepted: 23 September 2014 / Published: 26 September 2014
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 14632-14648
by , ,  and
Int. J. Mol. Sci. 2014, 15(8), 14632-14648; doi:10.3390/ijms150814632
Received: 20 June 2014 / Revised: 14 July 2014 / Accepted: 11 August 2014 / Published: 21 August 2014
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 14313-14331
by ,  and
Int. J. Mol. Sci. 2014, 15(8), 14313-14331; doi:10.3390/ijms150814313
Received: 12 June 2014 / Revised: 29 July 2014 / Accepted: 1 August 2014 / Published: 18 August 2014
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 5508-5521
by , , , , , ,  and
Int. J. Mol. Sci. 2014, 15(4), 5508-5521; doi:10.3390/ijms15045508
Received: 24 December 2013 / Revised: 25 February 2014 / Accepted: 6 March 2014 / Published: 31 March 2014
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
p. 4104-4125
by , , , , , , ,  and
Int. J. Mol. Sci. 2014, 15(3), 4104-4125; doi:10.3390/ijms15034104
Received: 13 December 2013 / Revised: 6 February 2014 / Accepted: 14 February 2014 / Published: 7 March 2014
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(This article belongs to the Special Issue Mechanism of Action and Applications of Cytokines in Immunotherapy)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Sex-hormone mediation of immune function as a driver of ME/CFS severity
Authors: Jeanna Harvey1,3, Melissa Hwang2, Saurabh Vashsishtha2, Zachary M Barnes1, 3 , Nancy G Klimas3, 4, Mary Ann Fletcher1,3, Gordon Broderick2,3
Affiliations: 1 Department of Medicine, University of Miami, Miami, FL, USA
2
Department of Medicine, University of Alberta, Edmonton, AB, Canada
3
Institute for Neuro Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
4
Miami Veterans Affairs Healthcare System, Miami, FL, USA
Abstract: Objectives. While biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are emerging, the mechanisms driving symptom severity remain poorly understood. We hypothesize that sex hormones and their mediation immune function may play a role. Our objective was to identify co-expression of cytokines and sex hormones that also coincide with changes in ME/CFS severity. Methods. As part of an ongoing study, blood samples were collected, at rest, from n=18 female ME/CFS subjects, who were 35-73 years of age. Illness severity was characterized using standard self-assessment instruments that included the multi-dimensional fatigue index (MFI), Beck Depression Index (BDI), and the short form 36 (SF-36). Blood samples were analyzed for concentrations of estradiol and progesterone, as well as for 16 cytokines, using a chemiluminescent assay.  Concentrations were log2 transformed and z scaled. Associations between symptoms and blood-borne markers were estimated, based on partial correlation, and adjusted for age and body mass index (BMI). Null probability estimates were based on an asymptotic normal distribution and adjusted for false discovery using Benjamini Hochberg criteria. Results. Analysis revealed direct and significant correlations (adjusted p<0.05) linking SF-36 measures for physical limit, emotional limit, and pain, with changes in progesterone (r=0.66), IL-4 (r=-0.71) and IL-1a (r=-0.76), respectively. The MFI measure for mental fatigue correlated positively with changes in IL-2 (r=0.62), while reduced motivation score correlated negatively with the interaction of progesterone and IL-17 (r=-0.63). In each case, symptoms correlating with blood-borne markers were directly part of a larger symptom cluster. Conclusion.  These preliminary results suggest that aspects of mental, emotional, and physical fatigue, including pain, correlate significantly with levels of progesterone, with that of specific Th1, Th2, and Th17, and with inflammatory cytokines. Importantly, the severity of a major symptom cluster may be driven by endocrine mediation of Th17 activity in ME/CFS.

Title: Th17 as a Potential Probiotic Therapeutic Target in Inflammatory Bowel Diseases
Authors: Eddy Owagaa and Jung-Su Changb,
Affiliations: a Institute of Food and Bioresources Technology, Dedan Kimathi University of Technology, Nyeri, Kenya. b School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan. R.O.C.To whom correspondence should be addressed. E-mail: susanchang@tmu.edu.tw; School of Nutrition and Health Sciences, College of Public Health and Nutrition,Taipei Medical University, Taipei, Taiwan, 250 Wu-Xing Street, Taipei 110, Taiwan, R.O.C; Tel.:+886-(2)27361661#6542, Fax:+886-(2)2737-3112
Abstract:
Inflammatory Bowel Diseases (IBD) are characterized by wasting and chronic intestinal inflammation. These symptoms are triggered by various cytokine-mediated pathways. In recent years, it has been shown that Th17 cells play a central role in the pathogenesis of IBD. Thus, Th17 cells are attractive therapeutic targets. Th17 cells preferentially produce IL-17, IL-17F, and IL-22 as signature cytokines. The role of the interplay between host genetics and intestinal microbiota in the pathogenesis of IBD has been demonstrated. Probiotics are live microorganisms that, when orally ingested in adequate amounts, confer a health benefit on the host by modulating enteric flora or by stimulating the local immune system. Several studies indicate the effectiveness of probiotics in the treatment of IBD (ulcerative colitis, pouchitis, and Crohn's disease). There is mounting evidence of probiotics selectively targeting the Th17 cell lineage during the the management of inflammatory and autoimmune diseases. This review highlights the critical role of Th17 cells in the pathogenesis of IBD and the rationale for using probiotics as novel therapeutic approaches in treating IBD through the manipulation of Th17 cells.
Keywords:
Th17; probiotics; Inflammatory Bowel Diseases; inflammation

Title: Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies
Authors: Boel De Paepe1, Jana Zschüntzsch2
Affiliations: 1Neuromuscular Reference Center, Laboratory for Neuropathology, Ghent University Hospital, Belgium 2Clinic for Neurology, University Medical Centre, Göttingen University, Germany
Abstract:
Idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of chronic disorders that includes dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (IBM), and necrotizing autoimmune myopathy (NAM). They represent distinct pathological entities but, most often, share the predominant symptom of inflammation in muscle tissue. Many of the immunopathogenic processes behind IIM remain poorly understood, but the crucial role played by cytokines as essential regulators of the intramuscular build-up of inflammation is undisputed. This review describes the extensive cytokine network inside IIM muscle. Patient tissues are characterized by the strong expression of subsets of Tumor Necrosis Factors (TNFa, LTb, BAFF), Interferons (IFNa/b/g), Interleukins (IL-1/6/12/15/18/23), and Chemokines (CXCL9/10/11/13, CCL2/3/4/8/19/21). Exploration of potential, disease modifying agents, based on the manipulation of the cytokine network, is provided. Reported responses to anti-TNFa treatment in IIM are conflicting, and the new onset of DM/PM has been described after administration of anti-TNFa agents for the treatment of other diseases. These studies point to the complex effects of TNFa neutralization. Treatment with the anti-IFNα monoclonal antibody has been shown to suppress the IFN type 1 gene signature in DM/PM patients and improve muscle strength. Beneficial effects of anti-IL-1 and anti-IL-6 therapy have also been reported. Understanding the interplay of cytokines in IIM will not only guide the development of therapeutic strategies, but might also inspire approaches for subtype patients and predict treatment outcomes.

Title: New Immunosuppressive Therapies in the Treatment of Uveitis
Authors: Salvador Mérida, Elena Palacios, Navea Amparo and Francisco Bosch Morell
Abstract: Uveitis is an inflammatory process that initially starts in the uvea, and can also affect other adjacent eye structures. It is currently the fourth leading cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequently necessary practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments against this disease include inhibitors or antibodies that act against these cytokines. Nevertheless, adequately treating each uveitis type entails a difficult therapeutic decision because no clear recommendations are found in the literature, given the dearth of protocolized clinical assays and case-control studies. This review aims to present the mechanisms and main indications of the most modern immunosuppressive drugs affecting cytokines.

Last update: 22 May 2015

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