SHP-1 (PTPN6) keeps the inflammation at bay: limiting IL-1α-mediated neutrophilic dermatoses by preventing Syk kinase activation
Journal
Cellular & molecular immunology
Journal Volume
14
Journal Issue
11
Pages
881
Date Issued
2017-07-10
Author(s)
You, Ren-In
Abstract
Autoinflammatory syndrome (AIS) is characterized by periodic inflammation in the absence of infection, autoantibodies or self-reactive lymphocytes. Therefore, AIS has defining characteristics that differ from those of autoimmune diseases. The sterile inflammation observed in AIS is likely caused by the dysregulation of the innate immune system. However, the etiologies and physiopathologies of these autoinflammatory disorders remain ambiguous. Uncontrolled interleukin (IL)-1 biosynthesis, which is initiated by danger signals in the inflammasome or via nucleic acid-sensing pathways, has been suggested to have a critical role in AISs such as Behçet’s disease, Familial Mediterranean fever and Cryopyrin-associated periodic syndrome. In addition, other proinflammatory cytokines, including TNF-α, Type-I interferons and IL-18, have been implicated in organ-specific inflammation in AISs. In clinical studies, colchicine and anti-TNF-α mAb have been used to treat AIS patients, and IL-1 blockade therapies (treatment with IL-1R inhibitor or anti-IL-1β mAb) significantly reduced disease progression and induced sustained remission in a substantial number of patients.1 Unfortunately, some patients still have poor responses to these therapies, and their diseases progress with multi-organ inflammation. Thus, scientists continue to search for new strategies with higher efficiency for AIS patients.
SDGs
Other Subjects
autoantibody; caspase 8; Fas associated death domain protein; interleukin 1alpha; interleukin 1beta converting enzyme; membrane protein; myeloid differentiation factor 88; phosphatidylinositol 4 phosphate kinase; protein kinase Syk; protein tyrosine phosphatase SHP 1; receptor interacting protein kinase 1; unclassified drug; acute febrile neutrophilic dermatosis; autoinflammatory disease; biosynthesis; bone marrow cell; cell viability; disease course; fibroblast; human; immune response; immunomodulation; innate immunity; missense mutation; nonhuman; Note; oxidative stress; protein analysis; protein degradation; protein function; protein phosphorylation; protein protein interaction; protein secretion; signal transduction
Publisher
CHIN SOCIETY IMMUNOLOGY
Type
journal article