Macrophage function of polarization of the body against the pathogen infection and the quality and efficiency of repair has an important role.
TSC1 / 2-mTOR pathway is important intracellular signaling pathways, the regulation of cell growth, development and metabolism of the cells have an important role. Specific deletion of TSC1 gene in mice transplanted Biology Research Group, Institute of Zoology, Chinese Academy application myeloid (TSC1KO) study found that, TSC1KO mice spontaneously with age, with severe autoimmune diseases, and the mouse Endotoxin inflammatory shock sensitive to sublethal doses of LPS can lead to death of the mice.
Experimental results show that, LPS or LPS combined IFN-γ-induced TSC1KO macrophages produce large amounts of pro-inflammatory cytokines TNF-α, IL-12 and iNOS, showed a stronger polarization of M1 macrophages. Biochemistry and molecular biology studies prove, TSC1 deletions caused by M1-type polarization enhancement is TSC1 / 2-RasGTPase-Raf-MEK-Erk pathway regulated by the mTOR-independent. In addition, in vivo experiments show that, TSC1KO the existence of anti-inflammatory macrophage polarization capability M2 type defects, manifested as the low expression of IL-4 stimulation of M2 marker of Arg1, Ym1 and Fizz, TSC1KO OVA-induced mice resistant asthma.
Further studies showed that, TSC1 by regulating the expression of mTOR-dependent C / EBPβ to regulate M2 macrophages type polarization. Thus, TSC1 / 2 protein complex through different signaling pathways to regulation of macrophage polarization to the regulation of homeostasis of macrophages, inhibition of macrophage inflammatory response, to avoid the occurrence of spontaneous inflammatory disease. The prevention of clinical research related to autoimmune diseases macrophages provides a new way of thinking. The research results in September 2014, published online in Nature Communications. Animals Zhu Lin Nan and co-first author Dr. Yang Tao was, Zhao Yong, a researcher for the corresponding author. The study with Professor Zhang Bing and Professor Zhang Lianfeng Concord and Nanjing University Zhongzhou Yang collaboration.This topic has been the Ministry of Science and the National Natural Science Foundation of funding.