Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Molecular Mechanisms of Sjögren's Syndrome
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Molecular Mechanisms of Sjögren's Syndrome

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 (28 February 2021) | Viewed by 20662

Special Issue Editor

Dr. Biji Theyilamannil Kurien

E-Mail Website
Guest Editor
The Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Interests: systemic lupus erythematosus; Sjögren’s syndrome; prolidase deficiency; free radical biology; experimental urolithiasis; curcumin and other curcuminoids; dietary supplements; microgravity
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sjögren’s syndrome (SS), a systemic autoimmune rheumatic disorder, is characterized by the B-cell infiltration of exocrine glands and the production of autoantibodies to self-antigens, such as Ro60 (SS-A), La (SS-B) and muscarinic 3 receptors. The most common symptoms of SS are dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia), and extreme tiredness. Additional symptoms include dryness of skin, nose, throat, vagina; arthralgias and myalgias, peripheral neuropathies, pulmonary, thyroid and renal disorders; and lymphoma. Increased tissue, serum cytokines and tissue fibrosis are also seen in SS subjects. Females account for 90% of all SS cases. Two age peaks have been identified for primary SS, the first after menarche (twenties to thirties), and the second following menopause (mid-fifties). SS can occur alone (primary SS) or along with another autoimmune disease (secondary SS), like systemic lupus erythematosus, rheumatoid arthritis, autoimmune hypothyroidism and systemic sclerosis. The molecular mechanisms mediating pathological dysfunction in SS remain to be elucidated, despite extensive studies investigating the underlying cause of Sjögren’s syndrome. There is no cure for Sjögren's syndrome currently, and treatment is mainly palliative.

In this Special Issue of IJMS, we are looking for articles that can pave the way to better understanding the molecular mechanisms mediating the pathological conditions of Sjögren’s syndrome. This would include articles that provide insights into molecular aspects of the initiation and progression of disease by glandular vascular endothelial cells, environmental triggers, free radical mediated oxidative damage, cytokine activation of lymphocytes, glandular lymphocyte and dendritic cell homing, the structure and function of autoantigens and autoantibody induction, germinal center-like structure formation, and the apoptosis of glandular cells. We also welcome review papers in these areas, as well as articles describing novel therapeutic targets and treatment options, new diagnostic tools, and biomarkers.

Dr. Biji Theyilamannil Kurien
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind 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 semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • autoimmunity
  • Sjögren’s syndrome
  • autoantibodies
  • salivary gland
  • lacrimal gland
  • dry eyes/mouth

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

32 pages, 5212 KiB  
Article
Two Be or Not Two Be: The Nuclear Autoantigen La/SS-B Is Able to Form Dimers and Oligomers in a Redox Dependent Manner
by Nicole Berndt, Claudia C. Bippes, Irene Michalk, Dominik Bachmann, Jennifer Bachmann, Edinson Puentes-Cala, Tabea Bartsch, Liliana R. Loureiro, Alexandra Kegler, Ralf Bergmann, Joanne K. Gross, Tim Gross, Biji T. Kurien, R. Hal Scofield, A. Darise Farris, Judith A. James, Marc Schmitz, Karim Fahmy, Anja Feldmann, Claudia Arndt and Michael P. Bachmannadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2021, 22(7), 3377; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073377 - 25 Mar 2021
Cited by 6 | Viewed by 2197
Abstract
According to the literature, the autoantigen La is involved in Cap-independent translation. It was proposed that one prerequisite for this function is the formation of a protein dimer. However, structural analyses argue against La protein dimers. Noteworthy to mention, these structural analyses were [...] Read more.
According to the literature, the autoantigen La is involved in Cap-independent translation. It was proposed that one prerequisite for this function is the formation of a protein dimer. However, structural analyses argue against La protein dimers. Noteworthy to mention, these structural analyses were performed under reducing conditions. Here we describe that La protein can undergo redox-dependent structural changes. The oxidized form of La protein can form dimers, oligomers and even polymers stabilized by disulfide bridges. The primary sequence of La protein contains three cysteine residues. Only after mutation of all three cysteine residues to alanine La protein becomes insensitive to oxidation, indicating that all three cysteines are involved in redox-dependent structural changes. Biophysical analyses of the secondary structure of La protein support the redox-dependent conformational changes. Moreover, we identified monoclonal anti-La antibodies (anti-La mAbs) that react with either the reduced or oxidized form of La protein. Differential reactivities to the reduced and oxidized form of La protein were also found in anti-La sera of autoimmune patients. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Sjögren's Syndrome)
►▼ Show Figures

Figure 1

12 pages, 2239 KiB  
Article
Formation of Autoimmune Lesions Is Independent of Antibiotic Treatment in NOD Mice
by Mami Sato, Rieko Arakaki, Hiroaki Tawara, Takaaki Tsunematsu and Naozumi Ishimaru
Int. J. Mol. Sci. 2021, 22(6), 3239; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063239 - 22 Mar 2021
Cited by 3 | Viewed by 2146
Abstract
The relationship between autoimmunity and changes in intestinal microbiota is not yet fully understood. In this study, the role of intestinal microbiota in the onset and progression of autoimmune lesions in non-obese diabetic (NOD) mice was evaluated by administering antibiotics to alter their [...] Read more.
The relationship between autoimmunity and changes in intestinal microbiota is not yet fully understood. In this study, the role of intestinal microbiota in the onset and progression of autoimmune lesions in non-obese diabetic (NOD) mice was evaluated by administering antibiotics to alter their intestinal microenvironment. Flow cytometric analysis of spleen cells showed that antibiotic administration did not change the proportion or number of T and B cells in NOD mice, and pathological analysis demonstrated that autoimmune lesions in the salivary glands and in the pancreas were also not affected by antibiotic administration. These results suggest that the onset and progression of autoimmunity may be independent of enteral microbiota changes. Our findings may be useful for determining the appropriate use of antibiotics in patients with autoimmune diseases who are prescribed drugs to maintain systemic immune function. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Sjögren's Syndrome)
►▼ Show Figures

Figure 1

14 pages, 1979 KiB  
Article
Chemokines Up-Regulated in Epithelial Cells Control Senescence-Associated T Cell Accumulation in Salivary Glands of Aged and Sjögren’s Syndrome Model Mice
by Mie Kurosawa, Yosuke Shikama, Masae Furukawa, Rieko Arakaki, Naozumi Ishimaru and Kenji Matsushita
Int. J. Mol. Sci. 2021, 22(5), 2302; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052302 - 25 Feb 2021
Cited by 4 | Viewed by 3274
Abstract
Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells [...] Read more.
Immunosenescence is characterized by age-associated changes in immunological functions. Although age- and autoimmune-related sialadenitis cause dry mouth (xerostomia), the roles of immunosenescence and cellular senescence in the pathogenesis of sialadenitis remain unknown. We demonstrated that acquired immune cells rather than innate immune cells infiltrated the salivary glands (SG) of aged mice. An analysis of isolated epithelial cells from SG revealed that the expression levels of the chemokine CXCL13 were elevated in aged mice. Senescence-associated T cells (SA-Ts), which secrete large amounts of atypical pro-inflammatory cytokines, are involved in the pathogenesis of metabolic disorders and autoimmune diseases. The present results showed that SA-Ts and B cells, which express the CXCL13 receptor CXCR5, accumulated in the SG of aged mice, particularly females. CD4+ T cells derived from aged mice exhibited stronger in vitro migratory activity toward CXCL13 than those from young mice. In a mouse model of Sjögren’s syndrome (SS), SA-Ts also accumulated in SG, presumably via CXCL12-CXCR4 signaling. Collectively, the present results indicate that SA-Ts accumulate in SG, contribute to the pathogenesis of age- and SS-related sialadenitis by up-regulating chemokines in epithelial cells, and have potential as therapeutic targets for the treatment of xerostomia caused by these types of sialadenitis. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Sjögren's Syndrome)
►▼ Show Figures

Figure 1

28 pages, 5829 KiB  
Article
T Cell Mediated Conversion of a Non-Anti-La Reactive B Cell to an Autoreactive Anti-La B Cell by Somatic Hypermutation
by Michael P. Bachmann, Tabea Bartsch, Claudia C. Bippes, Dominik Bachmann, Edinson Puentes-Cala, Jennifer Bachmann, Holger Bartsch, Claudia Arndt, Stefanie Koristka, Liliana R. Loureiro, Alexandra Kegler, Markus Laube, Joanne K. Gross, Tim Gross, Biji T. Kurien, R. Hal Scofield, A. Darise Farris, Judith A. James, Marc Schmitz and Anja Feldmann
Int. J. Mol. Sci. 2021, 22(3), 1198; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031198 - 26 Jan 2021
Cited by 9 | Viewed by 2606
Abstract
Since the first description of nuclear autoantigens in the late 1960s and early 1970s, researchers, including ourselves, have found it difficult to establish monoclonal antibodies (mabs) against nuclear antigens, including the La/SS-B (Sjögrens’ syndrome associated antigen B) autoantigen. To date, only a few [...] Read more.
Since the first description of nuclear autoantigens in the late 1960s and early 1970s, researchers, including ourselves, have found it difficult to establish monoclonal antibodies (mabs) against nuclear antigens, including the La/SS-B (Sjögrens’ syndrome associated antigen B) autoantigen. To date, only a few anti-La mabs have been derived by conventional hybridoma technology; however, those anti-La mabs were not bona fide autoantibodies as they recognize either human La specific, cryptic, or post-translationally modified epitopes which are not accessible on native mouse La protein. Herein, we present a series of novel murine anti-La mabs including truly autoreactive ones. These mabs were elicited from a human La transgenic animal through adoptive transfer of T cells from non-transgenic mice immunized with human La antigen. Detailed epitope and paratope analyses experimentally confirm the hypothesis that somatic hypermutations that occur during T cell dependent maturation can lead to autoreactivity to the nuclear La/SS-B autoantigen. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Sjögren's Syndrome)
►▼ Show Figures

Figure 1

Review

Jump to: Research

18 pages, 1453 KiB  
Review
SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome
by Margherita Sisto, Domenico Ribatti and Sabrina Lisi
Int. J. Mol. Sci. 2021, 22(6), 3203; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063203 - 21 Mar 2021
Cited by 19 | Viewed by 5519
Abstract
There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors [...] Read more.
There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjögren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS salivary glands (SGs) as mediator of the epithelial-mesenchymal transition (EMT) activation. Although EMT seems to cause pSS SG fibrosis, TGF-β family members have ambiguous effects on the function of pSS SGs. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Sjögren's Syndrome)
►▼ Show Figures

Figure 1

15 pages, 820 KiB  
Review
Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome
by Toshimasa Shimizu, Hideki Nakamura and Atsushi Kawakami
Int. J. Mol. Sci. 2021, 22(6), 3090; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063090 - 17 Mar 2021
Cited by 16 | Viewed by 3876
Abstract
Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. [...] Read more.
Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Sjögren's Syndrome)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop