In:
The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 144.22-144.22
Abstract:
Redox homeostasis in an inflammatory environment is crucial to ensure a balanced immune response. Several inflammatory disorders are associated with impairment of redox homeostasis, leading to DNA damage and subsequent immune dysregulation. The transcription factor STAT3 has anti-inflammatory activity in myeloid cells, mediated by inhibition of Ubc13, a key Toll-like receptor (TLR) signaling component. STAT3 anti-inflammatory activity is crucial in protection from systemic inflammation, maintenance of lineage-balanced hematopoiesis, and inhibition of DNA damage accumulation in hematopoietic progenitors. The molecular cues by which STAT3 mitigates DNA damage in an inflammatory environment, however, are poorly understood. Recently, we found that STAT3-deficient bone marrow derived-macrophages (BMDMs) exhibited increased oxidative stress upon TLR4 stimulation, including reduced antioxidant amounts and elevated production of reactive oxygen species (ROS). These responses were accompanied by increased gH2AX foci formation, suggesting accumulation of DNA damage. By contrast, BMDMs lacking Ubc13 exhibited increased expression of antioxidants and reduced DNA damage. RNA-sequencing analysis identified transcriptional targets of STAT3 and Ubc13 in steady state and TLR-stimulated BMDMs. Collectively, our findings suggest STAT3-mediated control of Ubc13 is important in regulating inflammation-induced oxidative stress and DNA damage by modulating antioxidant signaling and DNA damage repair pathways. Thus, STAT3 plays a crucial role in metabolic reprogramming of macrophages during inflammation to preserve redox homeostasis.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.204.Supp.144.22
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2020
detail.hit.zdb_id:
1475085-5
