1 Lab. of Stem Cell Stress, International Res. Center for Med. Sci., Kumamoto Univ. 2 Frontier Sci. Res. Center, Dept. of Biological Sci., Univ. of Miyazaki. 3 Center for Metabolic Regulation of Healthy Aging., Kumamoto Univ.Akkermansia muciniphila-derived factor induced extramedullary Bacterial infection often activates hematopoietic stem-and progenitor (HSPC) cells bone marrow (BM) and induces their migraiton towards spleen, defined as extramedullary hematopoiesis (EMH). Commensal mucin degrading Akkermansia muciniphila (A.m.), a major microbial species in human gut, can induce EMH, long-lasting anemia and chronic hepato-splenomegaly through cooperative TLR2 and IL-1R signals (Wang Y et al, EMBO Rep 2023). However, it remains unknown what molecule is responsible for this EMH.In this study, we aim to extract, isolate and identify the responsible molecule. WT-type and TLR2/4 KO mice were tested with known TLR2 & TLR4 ligand such as Pam3CSK4 and LPS, respectively, but neither alone nor in combination was able to reproduce EMH. Similarly, Amuc-1100, an outer membrane protein from A.m. known to activate TLR2, as well as LPS derived from Akkermansia, also failed to induce EMH. The approach with differential centrifugation and surfactants revealed that high-speed spin pellet (30K x g) could enrich the membrane fraction responsible for TLR2 stimulation in-vitro and splenomegaly in-vivo. Abundance of A.m. in the gut is known to correlate with efficiency of immuno-therapy but reversely correlates with survival of graft-versus-host disease and the occurrence of inflammatory bowel disease. Given the fact, identification of A.m.-derived component(s) and understanding of the underlying molecular mechanism of the inflammatory disorders will help to develop novel therapies for treatment.hematopoiesis (EMH)43 ○Md Naeem Hossain1 Yuxin wang1 Takuya Shiota2 Hitoshi Takizawa1,3P 013
元のページ ../index.html#46