Molecular Mechanisms Linking Inflammation to Autoimmunity in Sjögren’s Syndrome: Identification of New Targets

Sisto, Margherita; Ribatti, Doménico; Lisi, Sabrina

doi:10.3390/ijms232113229

Cited by 14 publications

(10 citation statements)

References 82 publications

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“…Some PYHIN factors were demonstrated to exert a critical function for exogenous DNA sensing, which can lead to the induction of IFNs and ISGs, or inflammasome regulation (30,31). Sustained activation of IFN-mediated cellular responses, in particular those associated with inflammation-induced cell death, are drivers of autoimmune disorders such as systemic lupus erythematosus, systemic sclerosis, and Sjögren's syndrome (32,33). The mechanisms controlling IFN production and ISG induction are therefore of paramount importance to regulate tissue homeostasis, innate and adaptive immune responses, and to sustain immune surveillance of tumours.…”

Section: The Pyhin Protein Family and Inflammationmentioning

confidence: 99%

MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes

Bottardi,

Layne,

Ramòn

et al. 2024

Front. Immunol.

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Inflammation control is critical during the innate immune response. Such response is triggered by the detection of molecules originating from pathogens or damaged host cells by pattern-recognition receptors (PRRs). PRRs subsequently initiate intra-cellular signalling through different pathways, resulting in i) the production of inflammatory cytokines, including type I interferon (IFN), and ii) the initiation of a cascade of events that promote both immediate host responses as well as adaptive immune responses. All human PYRIN and HIN-200 domains (PYHIN) protein family members were initially proposed to be PRRs, although this view has been challenged by reports that revealed their impact on other cellular mechanisms. Of relevance here, the human PYHIN factor myeloid nuclear differentiation antigen (MNDA) has recently been shown to directly control the transcription of genes encoding factors that regulate programmed cell death and inflammation. While MNDA is mainly found in the nucleus of leukocytes of both myeloid (neutrophils and monocytes) and lymphoid (B-cell) origin, its subcellular localization has been shown to be modulated in response to genotoxic agents that induce apoptosis and by bacterial constituents, mediators of inflammation. Prior studies have noted the importance of MNDA as a marker for certain forms of lymphoma, and as a clinical prognostic factor for hematopoietic diseases characterized by defective regulation of apoptosis. Abnormal expression of MNDA has also been associated with altered levels of cytokines and other inflammatory mediators. Refining our comprehension of the regulatory mechanisms governing the expression of MNDA and other PYHIN proteins, as well as enhancing our definition of their molecular functions, could significantly influence the management and treatment strategies of numerous human diseases. Here, we review the current state of knowledge regarding PYHIN proteins and their role in innate and adaptive immune responses. Emphasis will be placed on the regulation, function, and relevance of MNDA expression in the control of gene transcription and RNA stability during cell death and inflammation.

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Section: The Pyhin Protein Family and Inflammationmentioning

confidence: 99%

MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes

Bottardi,

Layne,

Ramòn

et al. 2024

Front. Immunol.

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“…Marked discoveries regarding the molecular mechanisms leading to SS have highlighted the role of angiogenesis ( 110 ), a fundamental process in growth and development ( 111 ). Previous experiments have shown that the metalloproteinase TNF-α-converting enzyme, which participates in proangiogenic pathways leading to the formation of vessels ( 112 , 113 ), is involved in VEGF/VEGFR2-mediated angiogenesis in SS ( 114 ).…”

Section: Influence Of Immune System and Angiogenesis In Endometriosis...mentioning

confidence: 99%

Association of endometriosis with Sjögren's syndrome: Genetic insights (Review)

Zervou,

Tarlatzis,

Grimbizis

et al. 2024

Int J Mol Med

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Patients with a history of endometriosis have an increased risk of developing various autoimmune diseases such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis and celiac disease. There is a potential association between endometriosis and an increased susceptibility for Sjögren's syndrome (SS). SS is a common chronic, inflammatory, systemic, autoimmune, multifactorial disease of complex pathology, with genetic, epigenetic and environmental factors contributing to the development of this condition. It occurs in 0.5-1% of the population, is characterized by the presence of ocular dryness, lymphocytic infiltrations and contributes to neurological, gastrointestinal, vascular and dermatological manifestations. Endometriosis is an inflammatory, estrogen-dependent, multifactorial, heterogeneous gynecological disease, affecting ≤10% of reproductive-age women. It is characterized by the occurrence of endometrial tissue outside the uterine cavity, mainly in the pelvic cavity, and is associated with pelvic pain, dysmenorrhea, deep dyspareunia and either subfertility or infertility. It is still unclear whether SS appears as a secondary response to endometriosis, or it is developed due to any potential shared mechanisms of these conditions. The aim of the present review was to explore further the biological basis only of the co-occurrence of these disorders but not their association at clinical basis, focusing on the analysis of the partially shared genetic background between endometriosis and SS, and the clarification of the possible similarities in the underlying pathogenetic mechanisms and the relevant molecular pathways.

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“…Sjogren's syndrome is a chronic autoimmune condition marked by persistent inflammation and impairment of exocrine gland function, particularly the lacrimal and salivary glands [128,129]. It primarily affects the moisture-producing glands, leading to symptoms such as dry eyes and dry mouth [130].…”

Section: Effects Of Tacrolimus On Dry Eye In Clinical Studiesmentioning

confidence: 99%

A comprehensive review of the effects of tacrolimus (FK-506) on dry eye disease (DED): Focus on inflammation and biochemical processes

Golmohammadi,

Ivraghi,

Jasim

et al. 2024

Preprint

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Dry eye disease (DED) represents a prevalent visual ailment, defined by insufficient wetting and lubrication of the ocular surface. The principal management strategy for dry eye involves the application of artificial tear solutions to mitigate eye discomfort. Moreover, immune-modulating agents such as cyclosporine A and tacrolimus (FK506) are employed in the therapeutic regimen for this condition. These drugs regulate the immune response and reduce ocular inflammation. Tacrolimus (TAC) is 10-100 times more effective than cyclosporine and has a better safety profile. Nevertheless, the modest aqueous solubility and substantial molecular size of TAC present obstacles to its efficient administration to the eye. Consequently, a range of TAC formulations including ointments, micelles, liposomes, and nanocarriers are under exploration to enhance ocular delivery. Findings from this investigation indicated that TAC impedes the secretion of pro-inflammatory cytokines and dampens immune activity by restraining the activation of T and B lymphocytes. Furthermore, TAC elevates goblet cell populations in the conjunctiva, pivotal for mucin production and the preservation of ocular surface integrity. Additionally, using TAC-loaded liposomes can further enhance its therapeutic efficacy by improving ocular bioavailability. Furthermore, 0.03% TAC eye drops applied directly to the eye successfully improve tear film stability and the health of the eye’s surface in patients with DED. Overall, TAC has shown promising effects in treating DED by reducing inflammation and improving tear secretion in experimental and clinical studies. However, more studies are needed to fully understand the mechanism of action and long-term effects of TAC on DED.

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Molecular Mechanisms Linking Inflammation to Autoimmunity in Sjögren’s Syndrome: Identification of New Targets

Cited by 14 publications

References 82 publications

MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes

MNDA, a PYHIN factor involved in transcriptional regulation and apoptosis control in leukocytes

Association of endometriosis with Sjögren's syndrome: Genetic insights (Review)

A comprehensive review of the effects of tacrolimus (FK-506) on dry eye disease (DED): Focus on inflammation and biochemical processes

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