Innate immunity in Sjögren's syndrome

Kiripolsky, Jeremy; McCabe, Liam G.; Kramer, Jill M.

doi:10.1016/j.clim.2017.04.003

Cited by 68 publications

(62 citation statements)

References 162 publications

(197 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Salivary gland inflammation is considered a hallmark of the disease (2), although the inciting disease events and pathways that maintain chronic inflammation in this tissue remain unknown. Several studies suggest that activation of innate immunity precedes the adaptive response in pSS (3)(4)(5)(6)(7)(8). However, the specific pathways that lead to disease initiation and progression are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Activation of Myd88-Dependent TLRs Mediates Local and Systemic Inflammation in a Mouse Model of Primary Sjögren's Syndrome

et al. 2020

Self Cite

View full text Add to dashboard Cite

Toll-like receptors (TLRs) are important mediators of chronic inflammation in numerous autoimmune diseases, although the role of these receptors in primary Sjögren's syndrome (pSS) remains incompletely understood. Previous studies in our laboratory established Myd88 as a crucial mediator of pSS, although the disease-relevant ligands and the upstream signaling events that culminate in Myd88 activation have yet to be established. The objective of this study was to identify specific Myd88-dependent TLR-related pathways that are dysregulated both locally and systemically in a mouse model of pSS [NOD.B10Sn-H2 b /J (NOD.B10)]. We performed RNA-sequencing on spleens derived from NOD.B10 mice. We then harvested salivary tissue and spleens from Myd88-sufficient and deficient C57BL/10 (BL/10) and NOD.B10 mice and performed flow cytometry to determine expression of Myd88-dependent TLRs. We cultured splenocytes with TLR2 and TLR4 agonists and measured production of inflammatory mediators by ELISA. Next, we evaluated spontaneous and TLR4-mediated inflammatory cytokine secretion in NOD.B10 salivary tissue. Finally, we assessed spontaneous Myd88-dependent cytokine secretion by NOD.B10 salivary cells. We identified dysregulation of numerous TLR-related networks in pSS splenocytes, particularly those employed by TLR2 and TLR4. We found upregulation of TLRs in both the splenic and salivary tissue from pSS mice. In NOD.B10 splenic tissue, robust expression of B cell TLR1 and TLR2 required Myd88. Splenocytes from NOD.B10 mice were hyper-responsive to TLR2 ligation and the endogenous molecule decorin modulated inflammation via TLR4. Finally, we observed spontaneous secretion of numerous inflammatory cytokines and this was enhanced following TLR4 ligation in female NOD.B10 salivary tissue as compared to males. The spontaneous production of salivary IL-6, MCP-1 and TNFα required Myd88 in pSS salivary tissue. Thus, our data demonstrate that Myd88-dependent TLR pathways contribute to the inflammatory landscape in pSS, and inhibition of such will likely have therapeutic utility.

show abstract

Section: Introductionmentioning

confidence: 99%

Activation of Myd88-Dependent TLRs Mediates Local and Systemic Inflammation in a Mouse Model of Primary Sjögren's Syndrome

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Sjögren's syndrome (SS) is a debilitating long-term chronic inflammatory/autoimmune disease in which moisture-generating exocrine gland tissues, such as the tear and salivary glands are primarily targeted by the immune system and is characterized by the development of dry mouth and dry eyes [ 59 139 ]. The hallmarks of SS are sicca symptoms, but various organ manifestations could also occur [ 140 ].…”

Section: Roles Of Inflammasomes In Inflammatory/autoimmune Diseasesmentioning

confidence: 99%

Role of inflammasomes in inflammatory autoimmune rheumatic diseases

2018

Korean J Physiol Pharmacol

View full text Add to dashboard Cite

Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin (IL)-1β and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and Sjögren's syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.

show abstract

“…The innate immune system is the first line of host defense and consists of several types of immune cells including dendritic cells (DC), macrophages, natural killer T cells (NK), and mast cells (MC). MSCs exhibit potent immunomodulatory effects on these cells which may play an important role in the pathogenesis of pSS [ 5 ]. Human BMSCs can suppress activation and maturation of DC and impair their antigen-presenting ability through the release of TSG-6 [ 61 – 63 ].…”

Section: Immunomodulatory Properties Of Mscs On Adaptive and Innatmentioning

confidence: 99%

“…Furthermore, approximately 5–10% of patients may develop lymphoma, mainly the mucosa-associated lymphoid tissue non-Hodgkin lymphoma, which represents the most severe complication of the disease [ 4 ]. Although the exact etiology is unclear, it is known that adaptive and innate immune cell imbalances are involved in the pathogenesis of pSS [ 5 – 7 ]. Current approaches such as traditional disease-modifying antirheumatic drugs and biologic agents do not cure this disease and have considerable side and toxic effects [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cells in Primary Sjögren’s Syndrome: Prospective and Challenges

Chen

Ma³

et al. 2018

Stem Cells International

View full text Add to dashboard Cite

Primary Sjögren's syndrome (pSS) is a chronic systemic inflammatory autoimmune disease characterized by lymphocytic infiltrates in exocrine glands. Current approaches do not control harmful autoimmune attacks or prevent irreversible damage and have considerable side effects. Mesenchymal stem cells (MSCs) have been effective in the treatment of several autoimmune diseases. The objective of this review is to illustrate the potential therapeutic role of MSCs in pSS. We summarize the recent advances in what is known about their immunomodulatory function and therapeutic applications in pSS. MSC transfusion can suppress autoimmunity and restore salivary gland secretory function in mouse models and patients with pSS by inducing regulatory T cells, suppressing Th1, Th17, and T follicular helper cell responses. In addition, MSCs can differentiate into salivary epithelial cells, presenting an option as a suitable alternative treatment. We also discuss current bioengineering methods which improve functions of MSCs for pSS. However, there remain many challenges to overcome before their wide clinical application.

show abstract

Innate immunity in Sjögren's syndrome

Cited by 68 publications

References 162 publications

Activation of Myd88-Dependent TLRs Mediates Local and Systemic Inflammation in a Mouse Model of Primary Sjögren's Syndrome

Activation of Myd88-Dependent TLRs Mediates Local and Systemic Inflammation in a Mouse Model of Primary Sjögren's Syndrome

Role of inflammasomes in inflammatory autoimmune rheumatic diseases

Mesenchymal Stem Cells in Primary Sjögren’s Syndrome: Prospective and Challenges

Contact Info

Product

Resources

About