LTBR-Pathway in Sjogren’s Syndrome: CXCL13 Levels and B-cell-Enriched Ectopic Lymphoid Aggregates in NOD Mouse Lacrimal Glands Are Dependent on LTBR

Fava, Roy A.; Browning, Jeffrey L.; Gatumu, Margaret Karimi; Skarstein, Kathrine; Bolstad, Anne-Isine

doi:10.1007/978-1-4419-6612-4_39

Cited by 13 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lymphotoxins (LTα, LTβ) and their receptors are part of the tumor necrosis factor superfamily (). Soluble LTα promotes production of IFNs and multiple chemokines that are important activating signals to the immune cells ().…”

Section: Discussionmentioning

confidence: 99%

Genome‐Wide DNA Methylation Patterns in Naive CD4+ T Cells From Patients With Primary Sjögren's Syndrome

Altorok

Coit

Hughes

et al. 2014

Arthritis & Rheumatology

159

102

View full text Add to dashboard Cite

Objective Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease with incompletely understood etiology. Very little is known about the role of epigenetic dysregulation in the pathogenesis of pSS. Methods We performed a genome-wide DNA methylation study in naïve CD4+ T cells in eleven pSS patients compared to age-, sex-, and ethnicity-matched healthy controls. Cytosine methylation was quantified using the Illumina Infinium HumanMethylation450 BeadChip array and validated using bisulfite sequencing. Results We identified 553 hypomethylated and 200 hypermethylated CpG sites in naïve CD4+ T cells from pSS patients compared to healthy matched controls, representing 311 hypomethylated and 115 hypermethylated gene regions. Hypomethylated genes in pSS include LTA, coding for Lymphotoxin α. Other relevant genes such as CD247, TNFRSF25, PTPRC, GSTM1 and PDCD1 were also hypomethylated. The interferon signature pathway was represented by hypomethylation of STAT1, IFI44L, USP18 and IFITM1. A group of genes encoding for members of the solute carrier proteins were differentially methylated. In addition, the transcription factor RUNX1 was hypermethylated in patients, suggesting a possible connection to lymphoma predisposition. Gene ontology (GO) analysis of hypomethylated genes demonstrated enrichment of genes involved in lymphocyte activation and immune response. GO terms for hypermethylated genes included antigen processing and presentation. Conclusion This is the first epigenome-wide DNA methylation study in pSS. Our data highlight a role for DNA methylation in pSS and identify disease-associated DNA methylation changes in several genes and pathways in naïve CD4+ T cells in pSS that may be involved in the pathogenesis of this disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome‐Wide DNA Methylation Patterns in Naive CD4+ T Cells From Patients With Primary Sjögren's Syndrome

Altorok

Coit

Hughes

et al. 2014

Arthritis & Rheumatology

159

102

View full text Add to dashboard Cite

show abstract

“…Cxcl13 and Ltβ were among the genes that were found differentially expressed in salivary glands of the NOD congenic mice compared to control mice. Furthermore, Ltβ blockade also reduced Cxcl13 in lacrimal glands of a NOD model of SS improving the corneal integrity [72, 73]. Recently, early BAFF receptor blockade was shown to mitigate murine SS [74•].…”

Section: Pathogenesismentioning

confidence: 99%

Epidemiology of Sjögren’s Syndrome—from an Oral Perspective

Bolstad

Skarstein

2016

Curr Oral Health Rep

Self Cite

View full text Add to dashboard Cite

Oral symptoms are among the most distressing manifestations for patients with Sjögren’s syndrome (SS). The feeling of dry mouth is unpleasant, and hyposalivation may contribute to difficulty in speaking, chewing and swallowing and reduced quality of life. Reduced salivary flow increases the risk for dental caries and problems with prosthetic replacement. It seems that SS is not as frequently occurring as previously anticipated. Population-based prevalence studies on primary SS in Europe, conducted on large background populations and in accordance with the AECG criteria, reported of a prevalence of 1–9 cases per 10,000 people. This gives a combined prevalence of nearly 39/100,000 (~0.04 %). The cause of Sjögren’s syndrome is even now not fully understood, and the treatment of oral symptoms is still mostly palliative. Hopefully, useful information will appear from the new methods that are now available for genome wide association studies, epigenetics, DNA methylation studies, and proteomics. Similarly, this is anticipated for the immunological side of the story. The interferon signature, the interferon γ/interferon α mRNA ratio, and CXCL13 are among the proposed biomarkers of active disease. In this review, we provide an update on oral aspects of Sjögren’s syndrome with emphasis on the latest publications on these topics.

show abstract

“…This would be an unappreciated property of epithelial surfaces, but would explain why many autoimmune disorders are characterized by lymphoid aggregation near epithelia, and would also highlight modulation of the LT receptor pathway as a new avenue of therapeutics for people with autoimmune diseases. For example, in a mouse model of Sjögren’s syndrome, lymphoid tissue aggregates form near the ductal epithelium as a result of CXCL13 overexpression, and the use of LTβR-Ig decreases lymphocyte recruitment to these sites 101 .…”

Section: Breaking (Mucosal) Barriers With the Lt Receptormentioning

confidence: 99%

Lymphotoxin signalling in immune homeostasis and the control of microorganisms

Upadhyay

2013

Nat Rev Immunol

109

View full text Add to dashboard Cite

Lymphotoxin (LT) is a member of the tumour necrosis factor (TNF) superfamily that was originally thought to be functionally redundant to TNF, but these proteins were later found to have independent roles in driving lymphoid organogenesis. More recently, LT mediated signalling has been shown to actively contribute to effector immune responses. LT regulates dendritic cell and CD4+ T cell homeostasis in the steady state and determines the functions of these cells during pathogenic challenges. The LT receptor pathway is essential for controlling pathogens and even contributes to the regulation of the intestinal microbiota, with recent data suggesting that LT induced changes in the microbiota promote metabolic disease. In this Review, we discuss these newly defined roles for LT, with a particular focus on how the LT receptor pathway regulates innate and adaptive immune responses to microorganisms.

show abstract

LTBR-Pathway in Sjogren’s Syndrome: CXCL13 Levels and B-cell-Enriched Ectopic Lymphoid Aggregates in NOD Mouse Lacrimal Glands Are Dependent on LTBR

Cited by 13 publications

References 24 publications

Genome‐Wide DNA Methylation Patterns in Naive CD4+ T Cells From Patients With Primary Sjögren's Syndrome

Genome‐Wide DNA Methylation Patterns in Naive CD4+ T Cells From Patients With Primary Sjögren's Syndrome

Epidemiology of Sjögren’s Syndrome—from an Oral Perspective

Lymphotoxin signalling in immune homeostasis and the control of microorganisms

Contact Info

Product

Resources

About