Dnase1L3 Regulates Inflammasome-Dependent Cytokine Secretion
| Autor: | Russell D. Salter, Guilan Shi, Wenbo Wu, Peter A. Keyel, Kennady N. Abbott |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy Dnase gamma Immunology Inflammation Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine systemic lupus erythematosus NLRC4 medicine Immunology and Allergy Propidium iodide Original Research autoimmunity Autoantibody Pyroptosis Inflammasome 3. Good health Cell biology cell activation macrophages 030104 developmental biology chemistry inflammation Cytokine secretion medicine.symptom Cell activation lcsh:RC581-607 030215 immunology medicine.drug |
| Zdroj: | Frontiers in Immunology, Vol 8 (2017) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2017.00522 |
| Popis: | Pediatric-onset systemic lupus erythematosus arises in humans and mice lacking the endonuclease Dnase1L3. When Dnase1L3 is absent, DNA from circulating apoptotic bodies is not cleared, leading to anti-DNA antibody production. Compared to early anti-DNA and anti-chromatin responses, other autoantibody responses and general immune activation in Dnase1L3−/− mice are greatly delayed. We investigated the possibility that immune activation, specifically inflammasome activation, is regulated by Dnase1L3. Here, we report that Dnase1L3 inhibition blocked both NLR family, pyrin domain containing 3 (NLRP3) and NLRC4 inflammasome-mediated release of high-mobility group box 1 protein and IL-1β. In contrast to IL-1β release, Dnase1L3 inhibition only mildly impaired NLRP3-dependent pyroptosis, as measured by propidium iodide uptake or LDH release. Mechanistically, we found that Dnase1L3 was needed to promote apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) nuclear export and speck formation. Our results demonstrate that Dnase1L3 inhibition separates cytokine secretion from pyroptosis by targeting ASC. These findings suggest that Dnase1L3 is necessary for cytokine secretion following inflammasome activation. |
| Databáze: | OpenAIRE |
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