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ISG15-Induced IL-10 Is a Novel Anti-Inflammatory Myeloid Axis Disrupted during Active Tuberculosis
- Source :
- Journal of Immunology, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2018, 200 (4), pp.1434-1442. ⟨10.4049/jimmunol.1701120⟩
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
Abstract
- The microarray data presented in this article have been submitted to the Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE80008. The online version of this article contains supplemental material.; International audience; IFN-stimulated gene 15 (ISG15) deficiency in humans leads to severe IFNopathies and mycobacterial disease, the latter being previously attributed to its extracellular cytokine-like activity. In this study, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique to primary human monocytes. A balanced ISG15-induced monocyte/IL-10 versus lymphoid/IFN-γ expression, correlating with p38 MAPK and PI3K signaling, was found using targeted in vitro and ex vivo systems analysis of human transcriptomic datasets. The specificity and MAPK/PI3K-dependence of ISG15-induced monocyte IL-10 production was confirmed in vitro using CRISPR/Cas9 knockout and pharmacological inhibitors. Moreover, this ISG15/IL-10 axis was amplified in leprosy but disrupted in human active tuberculosis (TB) patients. Importantly, ISG15 strongly correlated with inflammation and disease severity during active TB, suggesting its potential use as a biomarker, awaiting clinical validation. In conclusion, this study identifies a novel anti-inflammatory ISG15/IL-10 myeloid axis that is disrupted in active TB.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Myeloid
[SDV]Life Sciences [q-bio]
education
Immunology
Inflammation
03 medical and health sciences
0302 clinical medicine
medicine
Immunology and Allergy
Humans
Tuberculosis
Ubiquitins
business.industry
Monocyte
ISG15
3. Good health
Interleukin-10
Interleukin 10
030104 developmental biology
medicine.anatomical_structure
Cancer research
Leukocytes, Mononuclear
Biomarker (medicine)
Cytokines
medicine.symptom
business
Ex vivo
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 00221767 and 15506606
- Database :
- OpenAIRE
- Journal :
- Journal of Immunology, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2018, 200 (4), pp.1434-1442. ⟨10.4049/jimmunol.1701120⟩
- Accession number :
- edsair.doi.dedup.....27a9fc2767d4da3d952c647d894b6ef9