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The Role of Nucleic Acids in Normal and Aberrant Immunity

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

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 8026

Special Issue Editor


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Guest Editor
1. Department of Medicine and Immunology, Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC 27710, USA
2. Medical Research Service, Veterans Administration Medical Center, Durham, NC 27705, USA
Interests: immune properties of DNA; immunochemical properties of anti-DNA antibodies; the properties of antinuclear antibodies; the role of DNA in the pathogenesis of systemic lupus erythematosus; the role of microparticles as a source of extracellular DNA; immune properties of HMGB1
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Special Issue Information

Dear Colleagues,

DNA and RNA have diverse biological activities that include the activation of immune responses in normal and aberrant immunity. These activities depend on intracellular nucleic acid sensors which can be stimulated by nucleic acids present in the cytoplasm of cells due to intracellular infection or due to cell stress and injury. In addition, nucleic acids from the extracellular space can enter innate immune cells in the form of immune complexes formed by antibodies to DNA or antibodies to RNA binding proteins with which the RNA is associated. For this reason, DNA and RNA can play a key role in host defense to infection as well as the pathogenesis of autoimmune and inflammatory diseases such as systemic lupus erythematosus (SLE); SLE is characterized by antibodies to nuclear molecules (antinuclear antibodies or ANAs). The role of nucleic acids as endogenous and exogenous stimulators of innate immunity has broad relevance in medicine and is leading to the development of immunomodulatory approaches for increasing or decreasing the amount and activity of DNA and RNA in the system in various diseases. This Special Issue will include cutting-edge articles on the following topics: the structure of DNA and RNA with respect to immune activity; the DNA and RNA sensors responding to cytoplasmic nucleic acids; the role of intracellular and extracellular nucleases in the response to DNA and RNA; antinuclear antibodies; the role of immune complexes in driving cytokine production; the role of mitochondrial DNA in immune activation; the generation of extracellular cell free (cf) DNA; the role of extracellular nucleic acids as biomarkers; and the role of DNA and RNA in driving disease pathogenesis.

Prof. Dr. David Stephen Pisetsky
Guest Editor

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Keywords

  • DNA
  • RNA
  • nucleases
  • toll-like receptors
  • cGAS/STING
  • cell free DNA

Published Papers (3 papers)

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14 pages, 15804 KiB  
Article
Anti-DNA-IgM Favors the Detection of NET-Associated Extracellular DNA
by Han Wang, Antonia Margarethe Stehr, Jeeshan Singh, Leticija Zlatar, Arndt Hartmann, Katja Evert, Elisabeth Naschberger, Saskia von Stillfried, Peter Boor, Luis E. Muñoz, Jasmin Knopf, Michael Stürzl and Martin Herrmann
Int. J. Mol. Sci. 2023, 24(4), 4101; https://doi.org/10.3390/ijms24044101 - 17 Feb 2023
Cited by 1 | Viewed by 2325
Abstract
During inflammatory responses, neutrophils enter the sites of attack where they execute various defense mechanisms. They (I) phagocytose microorganisms, (II) degranulate to release cytokines, (III) recruit various immune cells by cell-type specific chemokines, (IV) secrete anti-microbials including lactoferrin, lysozyme, defensins and reactive oxygen [...] Read more.
During inflammatory responses, neutrophils enter the sites of attack where they execute various defense mechanisms. They (I) phagocytose microorganisms, (II) degranulate to release cytokines, (III) recruit various immune cells by cell-type specific chemokines, (IV) secrete anti-microbials including lactoferrin, lysozyme, defensins and reactive oxygen species, and (V) release DNA as neutrophil extracellular traps (NETs). The latter originates from mitochondria as well as from decondensed nuclei. This is easily detected in cultured cells by staining of DNA with specific dyes. However, in tissues sections the very high fluorescence signals emitted from the condensed nuclear DNA hamper the detection of the widespread, extranuclear DNA of the NETs. In contrast, when we employ anti-DNA-IgM antibodies, they are unable to penetrate deep into the tightly packed DNA of the nucleus, and we observe a robust signal for the extended DNA patches of the NETs. To validate anti-DNA-IgM, we additionally stained the sections for the NET-markers histone H2B, myeloperoxidase, citrullinated histone H3, and neutrophil elastase. Altogether, we have described a fast one-step procedure for the detection of NETs in tissue sections, which provides new perspectives to characterize neutrophil-associated immune reactions in disease. Full article
(This article belongs to the Special Issue The Role of Nucleic Acids in Normal and Aberrant Immunity)
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Review

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22 pages, 1985 KiB  
Review
The Involvement of Alarmins in the Pathogenesis of Sjögren’s Syndrome
by Julie Sarrand, Laurie Baglione, Dorian Parisis and Muhammad Soyfoo
Int. J. Mol. Sci. 2022, 23(10), 5671; https://doi.org/10.3390/ijms23105671 - 18 May 2022
Cited by 9 | Viewed by 2374
Abstract
Sjögren’s syndrome (SS) is a chronic autoimmune disease that affects exocrine glands, primarily the salivary and lachrymal glands. It is characterized by lymphoplasmacytic infiltration of the glandular tissues, ultimately leading to their dysfunction and destruction. Besides classic dry eyes and dry mouth defined [...] Read more.
Sjögren’s syndrome (SS) is a chronic autoimmune disease that affects exocrine glands, primarily the salivary and lachrymal glands. It is characterized by lymphoplasmacytic infiltration of the glandular tissues, ultimately leading to their dysfunction and destruction. Besides classic dry eyes and dry mouth defined as sicca syndrome, patients affected by the disease also typically display symptoms such as fatigue, pain and in more than 50% of cases, systemic manifestations such as arthritis, interstitial lung involvement, neurological involvement and an increased risk of lymphoma. The pathophysiological mechanisms underlying SS still remain elusive. The crucial role of innate immunity has been advocated in recent years regarding the pathogenesis of pSS, especially in the initiation and progression toward autoimmunity. Alarmins are endogenous molecules that belong to the large family of damage associated molecular pattern (DAMP). Alarmins are rapidly released, ensuing cell injury and interacting with pattern recognition receptors (PRR) such as toll-like receptors (TLR) to recruit and activate cells of the innate immune system and to promote adaptive immunity responses. This review highlights the current knowledge of various alarmins and their role in the pathogenesis of pSS. Full article
(This article belongs to the Special Issue The Role of Nucleic Acids in Normal and Aberrant Immunity)
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9 pages, 747 KiB  
Review
The Interaction of Anti-DNA Antibodies with DNA: Evidence for Unconventional Binding Mechanisms
by David S. Pisetsky, Angel Garza Reyna, Morgan E. Belina and Diane M. Spencer
Int. J. Mol. Sci. 2022, 23(9), 5227; https://doi.org/10.3390/ijms23095227 - 7 May 2022
Cited by 3 | Viewed by 2454
Abstract
Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus, a prototypic autoimmune disease. These antibodies bind to conserved sites on single-stranded and double-stranded DNA and display variable region somatic mutations consistent with antigen selection. Nevertheless, the interaction of anti-DNA with [...] Read more.
Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus, a prototypic autoimmune disease. These antibodies bind to conserved sites on single-stranded and double-stranded DNA and display variable region somatic mutations consistent with antigen selection. Nevertheless, the interaction of anti-DNA with DNA has unconventional features. Anti-DNA antibodies bind by a mechanism called monogamous bivalency, in which stable interaction requires contact of both Fab sites with determinants on the same extended DNA molecule; the size of this DNA can be hundreds to thousands of bases, especially in solid phase assays. This binding also requires the presence of the Fc portion of IgG, a binding mechanism known as Fc-dependent monogamous bivalency. As shown by the effects of ionic strength in association and dissociation assays, anti-DNA binding is primarily electrostatic. Like anti-DNA autoantibodies, anti-DNA antibodies that bind specifically to non-conserved sites on bacterial DNA, a type of anti-DNA found in otherwise healthy individuals, also interact by monogamous bivalency. The unconventional features of anti-DNA antibodies may reflect the highly charged and polymeric nature of DNA and the need for molecular rearrangements to facilitate monogamous bivalency; the Fc portion contributes to binding in an as yet unknown way. Full article
(This article belongs to the Special Issue The Role of Nucleic Acids in Normal and Aberrant Immunity)
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