Aberrant macrophages, central to discoid lupus erythematosus?
Immunology
Final Report Abstract
In the present project, I investigated 1) how macrophage cytokine IL-34 contributes to the acute kidney injury and the transition from acute kidney injury and 2) aberrant macrophages poised to destroy drive autoimmune diseases. Thereby, we could show that IL-34 mediates acute kidney injury and worsens subsequent chronic kidney disease via two distinct mechanisms: (i) enhancing intra-renal macrophage proliferation and (ii) elevating bone marrow myeloid cell proliferation, thereby increasing circulating monocytes that are drawn into the kidney by chemokines. In addition, we found out that macrophages accumulate and proliferate adjacent to necrotic muscle fibers in skeletal muscles with dysferlinopathy, and proliferating macrophages express pro-inflammatory mediators (e.g. TNF-α, NO) in inflamed muscles of BLA/J mice (8 and 14 mo of age). Our findings from the studies on the role of IL-34 were highly translational as: (i) kidney transplants subject to kidney ischemia and reperfusion express IL-34, c-fms and PTP-ζ in tubular epithelial cells during acute kidney injury that increases with advancing injury and (ii) IL-34 expression rises with increasing ischemia in donor kidneys. In our study, we identified IL-34 as a strong target for the treatment of acute kidney injury and chronic kidney disease. Our results were also noticed with high attention. Thus, our results were highlighted in Nature Review Nephrology in 2015. Likewise, the results from the studies on the role of macrophages in dysferlinopathy will be translational.
Publications
- (2015). IL-34 Mediates Acute Kidney Injury Worsening Subsequent Chronic Kidney Disease. Journal of Clinical Investigation, 125(8):3198-214
ea-Hyun Baek, Rui Zeng, Julia Weinmann- Menke, Todd Valerius, Yukihiro Wada, Ajay K. Amrendra, Marco Colonna, Vicki R. Kelley
(See online at https://doi.org/10.1172/JCI81166) - (2015). The Clash of Langerhans Cell Homeostasis in Skin: Should I stay or should I go? Seminars in Cell and Developmental Biology, 41: 30 - 8
Thomas Hieronymus, Martin Zenke, Jea-Hyun Baek, Kirstin Seré
(See online at https://doi.org/10.1016/j.semcdb.2014.02.009)
