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Kunze, F.A.* ; Bauer, M.* ; Komuczki, J.* ; Lanzinger, M.* ; Gunasekera, K.* ; Hopp, A.K.* ; Lehmann, M. ; Becher, B.* ; Müller, A.* ; Hottiger, M.O.*

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)
Verlagsversion Postprint DOI PMC
Open Access Green
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Nf-kappa-b; Poly(adp-ribose) Polymerase-1; Expression; Coactivator; Prevents; Invasion; Parp-1; Roles
ISSN (print) / ISBN 0022-1767
e-ISSN 1550-6606
Zeitschrift Journal of Immunology
Quellenangaben Band: 202, Heft: 5, Seiten: 1406-1416 Artikelnummer: , Supplement: ,
Verlag American Association of Immunologists
Verlagsort 9650 Rockville Pike, Bethesda, Md 20814 Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Lung Repair and Regeneration (LRR)