Genetics of systemic lupus erythematosus and Sjögren's syndrome: an update

Teruel, María; Alarcón‐Riquelme, Marta E.

doi:10.1097/bor.0000000000000310

Cited by 47 publications

(40 citation statements)

References 92 publications

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“…As expected from the genetic similarities between SLE and SS (Teruel and Alarcon-Riquelme, 2016), we confirmed that T cells from patients with SS, like SLE, were poorer responders to allogenic non-T cells than T cells from healthy donors (Russell et al., 1983). Furthermore, we could evaluate M3R-reactive CD4+ T cells, which are thought to be one of the pathogenic T cells for SS.…”

Section: Discussionsupporting

confidence: 88%

Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell Clones of Sjögren's Syndrome

Iizuka‐Koga

Asashima

Lai³

et al. 2017

Stem Cell Reports

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SummaryAlthough it is important to clarify the pathogenic functions of T cells in human samples, their examination is often limited due to difficulty in obtaining sufficient numbers of dendritic cells (DCs), used as antigen-presenting cells, especially in autoimmune diseases. We describe the generation of DCs from induced pluripotent stem cells derived from T cells (T-iPSCs). We reprogrammed CD4+ T cell clones from a patient with Sjögren's syndrome (SS) into iPSCs, which were differentiated into DCs (T-iPS-DCs). T-iPS-DCs had dendritic cell-like morphology, and expressed CD11c, HLA-DR, CD80, CD86, and also BDCA-3. Compared with monocyte-derived DCs, the capacity for antigen processing was similar, and T-iPS-DCs induced the proliferative response of autoreactive CD4+ T cells. Moreover, we could evaluate T cell functions of the patient with SS. In conclusion, we obtained adequate numbers of DCs from T-iPSCs, which could be used to characterize pathogenic T cells in autoimmune diseases such as SS.

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Section: Discussionsupporting

confidence: 88%

Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell Clones of Sjögren's Syndrome

Iizuka‐Koga

Asashima

Lai³

et al. 2017

Stem Cell Reports

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“…A possible explanation for the fact that NETs lead to the activation of self-reactive B cells that produce Abs against NETs in LE patients but not in healthy donors is that LE patients have a genetically determined tendency for increased B cell activation. In fact, susceptibility genes involving B cell function and signaling, including BANK, BLK, and LYN, have been found in LE patients (20). Other susceptibility genes include genes involved in type I IFN signaling, such as TLR7, IRF5, TYK2, STAT4, IFIH1, TREX, and STING (20), which may decrease the threshold for B cell activation in LE.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, susceptibility genes involving B cell function and signaling, including BANK, BLK, and LYN, have been found in LE patients (20). Other susceptibility genes include genes involved in type I IFN signaling, such as TLR7, IRF5, TYK2, STAT4, IFIH1, TREX, and STING (20), which may decrease the threshold for B cell activation in LE. As a consequence, the break of B cell tolerance leads to the production of anti-NET Abs that further promote NET formation (5) and decrease NET degradation in LE (13)(14)(15), providing a feedback loop that sustains the inflammatory process.…”

Section: Discussionmentioning

confidence: 99%

Netting Neutrophils Activate Autoreactive B Cells in Lupus

Gestermann

Domizio

Lande³

et al. 2018

The Journal of Immunology

136

124

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Lupus erythematosus (LE) patients develop autoantibodies that form circulating immune complexes (ICs) with extracellular self-nucleic acids. These ICs are deposited into peripheral tissues, where they trigger detrimental organ inflammation. Recent evidence suggests that ICs contain LL37-DNA complexes derived from neutrophil extracellular traps (NETs) and that LE patients develop pathogenic autoantibodies against these structures, including Abs to LL37. However, the mechanism that leads to the generation of these Abs is unknown. In this study, we show that NETs directly trigger Ab production by human memory B cells. This occurs via LL37-DNA complexes present in NETs, which have the unique ability to gain access to endosomal compartments of B cells and to trigger TLR9 activation. In LE patients, NET-derived LL37-DNA complexes trigger polyclonal B cell activation via TLR9, but also specifically expand self-reactive memory B cells producing anti-LL37 Abs in an Ag-dependent manner. These findings suggest a unique link between neutrophils and B cells in which NETs trigger a concerted activation of TLR9 and BCR leading to anti-NET autoantibody production in lupus.

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“…There are more than 15 robust susceptibility loci identified for SS and many of these are shared with SLE [33]. Similar to SLE, patients with SS display increased expression of type I and type II IFN-regulated genes in both salivary tissue and peripheral blood [19, 30, 34–38].…”

Section: Genetic Studies In Pss Patients Identify Polymorphisms Inmentioning

confidence: 99%

Innate immunity in Sjögren's syndrome

Kiripolsky

McCabe

Kramer

2017

Clinical Immunology

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Sjögren’s syndrome (SS) is an autoimmune disease of exocrine tissue that primarily affects women. Although patients typically experience xerostomia and xerophthalmia, numerous systemic disease manifestations are seen. Innate immune hyperactivity is integral to many autoimmune diseases, including SS. Results from SS mouse models suggest that innate immune dysregulation drives disease and this is a seminal event in SS pathogenesis. Findings in SS patients corroborate those in mouse models, as innate immune cells and pathways are dysregulated both in exocrine tissue and in peripheral blood. We will review the role of the innate immune system in SS pathogenesis. We will discuss the etiology of SS with an emphasis on innate immune dysfunction. Moreover, we will review the innate cells that mediate inflammation in SS, the pathways implicated in disease, and the potential mechanisms governing their dysregulation. Finally, we will discuss emerging therapeutic approaches to target dysregulated innate immune signaling in SS.

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Genetics of systemic lupus erythematosus and Sjögren's syndrome: an update

Cited by 47 publications

References 92 publications

Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell Clones of Sjögren's Syndrome

Functional Analysis of Dendritic Cells Generated from T-iPSCs from CD4+ T Cell Clones of Sjögren's Syndrome

Netting Neutrophils Activate Autoreactive B Cells in Lupus

Innate immunity in Sjögren's syndrome

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