Abstract:
:Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with a broad spectrum of clinical presentations and association with multiple immunological abnormalities. Recent research of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway-revealed aberrant STAT signaling in inflammatory conditions and autoimmune diseases including SLE. STAT proteins are major components in interferon (IFN)-dependent gene expression and are responsible for signal transduction of over 50 cytokines, hormones, and growth factors regulating key cellular processes such as survival, proliferation, and differentiation. This review summarizes the present evidence from experimental animal models and patients with SLE for the involvement of STAT pathways in the pathogenesis of SLE underlining the role of different members of the STAT family. Genome-wide association studies provided evidence that variations in STAT4 gene are linked to the development of SLE in humans. First integration with genome-wide epigenomics data suggests that control of CD4+ T cell differentiation in which STATs play a major role may be an important component of the genetic contribution to disease susceptibility. Increased transcript and total protein STAT1 levels were described both in SLE T and B cells suggestive of the priming mechanisms that augment STAT1 signaling responses to IFN. STAT3 has a crucial role in Th17 differentiation, T follicular helper, and B cells, and STAT3 inhibition could represent a possible future therapeutic target in SLE. STAT5B appears to act as a critical modulator of human Treg development and function. While the imbalance between phosphorylated STAT5 and STAT3 in human SLE T cells was implicated in dysregulated IL-10 expression, Treg-specific deletion of STAT3 in mouse model even enhanced Th17-mediated inflammation. Finally, we present also a comprehensive analysis of studies investigating STAT signaling responses in conventional and regulatory subsets of SLE T and B cells and possible implications of STAT inhibition for clinical therapy.
journal_name
Clin Rev Allergy Immunoljournal_title
Clinical reviews in allergy & immunologyauthors
Goropevšek A,Holcar M,Avčin Tdoi
10.1007/s12016-016-8550-ysubject
Has Abstractpub_date
2017-04-01 00:00:00pages
164-181issue
2eissn
1080-0549issn
1559-0267pii
10.1007/s12016-016-8550-yjournal_volume
52pub_type
杂志文章,评审abstract::The Zika virus outbreaks highlight the growing importance need for a reliable, specific and rapid diagnostic device to detect Zika virus, as it is often recognized as a mild disease without being identified. Many Zika virus infection cases have been misdiagnosed or underreported because of the non-specific clinical pr...
journal_title:Clinical reviews in allergy & immunology
pub_type: 杂志文章,评审
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journal_title:Clinical reviews in allergy & immunology
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journal_title:Clinical reviews in allergy & immunology
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doi:10.1007/s12016-020-08784-8
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journal_title:Clinical reviews in allergy & immunology
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doi:10.1007/BF02737598
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pub_type: 杂志文章,评审
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journal_title:Clinical reviews in allergy & immunology
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journal_title:Clinical reviews in allergy & immunology
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