Protein NBS1, which plays a key role in DNA damage repair, is required for macrophage functional activity. This is one of the conclusions of a scientific paper published in the journal Blood -- considered one of the best scientific publications in the field of haematology -- and signed by a team of experts from the Faculty of Biology of the University of Barcelona (UB), the Barcelona Science Park (PCB) and the Institute for Research in Biomedicine (IRB Barcelona). The protein also has implications for understanding the immune defects observed in patients with Nijmegen breakage syndrome and other related disorders.
The article is signed by Selma Pereira Lopes, Juan Tur, Juan Antonio Calatayud-Subias, Jorge Lloberas and Antonio Celada, experts in the Department of Physiology and Immunology (Faculty of Biology of the UB and PCB), who are members of the Consolidated Research Group Macrophage Biology, and Travis H. Stracker, researcher at the IRB Barcelona.
When proteins are not able to repair DNA
Protein NBS1 (Nijmegen breakage syndrome 1) is a component of the MRE11 complex, which is a sensor of DNA double-strand breaks and plays a crucial role in the DNA damage response and cell signalling. In the new study, the scientific team has examined the role of NBSI in macrophage function. Macrophages are immune system cells able to produce great quantities of reactive oxygen species that can damage DNA. The study has been developed with a knockout (KO) mouse model genetically modified to not express the gene that codifies protein NBS1.
According to results, when macrophages are activated by pro-inflammatory (IFN-γ and LPS) stimuli, NBS1 absence produces DNA breaks, which causes defects in proliferation, delayed differentiation and increased senescence. Moreover, these cells show an increased expression of pro-inflammatory cytokines, molecules that favour autoimmune processes and disorders in in vivo models of inflammatory diseases.
The article published in the journal Blood provides new insights into the role that macrophages play in severe immunodeficiency in patients with Nijmegen breakage syndrome and similar diseases.
The Consolidated Research Group Macrophage Biology, led by Antonio Celada, professor in the Department of Physiology and Immunology, is focused on studying the role that macrophages play in inflammation, one of the keys of immune response (elimination of bacteria, virus, parasites, tumour cells, etc.).
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