The Function And Mechanism Study OF Cullin3 In Regulating Myeloid Cell Functions

Myeloid cells are very important components of immune system and are crucial to human health.The function of myeloid cells are tightly controlled in the body.Myeloid cells activities are strictly regulated at the level of transcription and some signalling pathways are proved to be important in myeloid cells,however,how protein translational modification system,especially ubiquitination,regulates myeloid cells functions remains unknown.E3 ubiquitin ligase Cullin3 plays key roles in human physiology and pathology.The function of Cullin3 in regulating lymphoid cell have been well established,however,the role of Cullin3 in myeloid cells is still unknown.Here we report Cullin3 is an important regulator in myeloid cells and play important roles in inflammation and tumor.Our preliminary data indicated that Cullin3 orchestrates macrophage polarization via regulating STAT signaling pathway and Cullin3 also regulates neutrophil infiltration.Compared with WT mice,Myloied-specific Culiin3 knock-out mice are prone to promote tumor growth and metastasis,accompanied by more M2 macrophage and less neutrophil infiltration in tumor.We also found that Mice with Cullin3 deficient myeloid cells were more resistant to developing DSS-induced colitis as evidenced by lower clinical,histopathologic and pathologic scores.We plan to clarify the detailed mechanisms by which Cullin3 regulate myeloid cell function and shed more light on Cullin3 as a potential target for cancer and inflammation treatment.Although we have shown that Cullin3 regulates macrophage polarization and neutrophil infiltration,some questions have yet to be answered.For example,Can Cullin3 regulate neutrophil polarization and killing function?Can Cullin3 promote pre-metastatic niche formation by regulating myeloid cell functions?What's the detailed mechanism of Cullin3 in regulating myeloid cell functions?Research should be performed to answer these questions.Collectively,our results identify Cullin3 as a previously unknown regulator in myeloid cells to control tumor growth and metastasis and inflammation disease.