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ARTD1 in myeloid cells controls the IL-12/18-IFN-γ axis in a model of sterile sepsis, chronic bacterial infection, and cancer.
J. Immunol. 202, 1406-1416 (2019)
Mice deficient for ADP-ribosyltransferase diphteria toxin-like 1 (ARTD1) are protected against microbially induced inflammation. To address the contribution of ARTD1 to inflammation specifically in myeloid cells, we generated an Artd1(Delta Myel) mouse strain with conditional ARTD1 deficiency in myeloid lineages and examined the strain in three disease models. We found that ARTD1, but not its enzymatic activity, enhanced the transcriptional activation of distinct LPS-induced genes that included IL-12, TNF-alpha, and IL-6 in primary bone marrow derived macrophages and LPS-induced IL-12/18-IFN-gamma signaling in Artd1(Delta Myel) mice. The loss of Artd1 in myeloid cells also reduced the T(H)1 response to Helicobacter pylori and impaired immune control of the bacteria. Furthermore, Artd1(Delta Myel) mice failed to control tumor growth in a s.c. MC-38 model of colon cancer, which could be attributed to reduced T(H)1 and CD8 responses. Together, these data provide strong evidence for a cell-intrinsic role of ARTD1 in myeloid cells that is independent of its enzymatic activity and promotes type I immunity by promoting IL-12/18 expression.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Nf-kappa-b; Poly(adp-ribose) Polymerase-1; Expression; Coactivator; Prevents; Invasion; Parp-1; Roles
Language
english
Publication Year
2019
HGF-reported in Year
2019
ISSN (print) / ISBN
0022-1767
e-ISSN
1550-6606
Journal
Journal of Immunology
Quellenangaben
Volume: 202,
Issue: 5,
Pages: 1406-1416
Publisher
American Association of Immunologists
Publishing Place
9650 Rockville Pike, Bethesda, Md 20814 Usa
Reviewing status
Peer reviewed
Institute(s)
Institute of Lung Health and Immunity (LHI)
POF-Topic(s)
80000 - German Center for Lung Research
Research field(s)
Lung Research
PSP Element(s)
G-501800-311
WOS ID
WOS:000459022800011
Scopus ID
85061861460
PubMed ID
30674576
Erfassungsdatum
2019-03-19