Yuan Jiang’s research while affiliated with Air Force Medical University and other places

Natural killer cell-based immunotherapy has become a leading-edge tool against cancer, but still faces a variety of challenges, such as phenotype shift and dysfunction of NK cells in tumor microenvironment. Thus, finding potent agents that could inhibit the phenotype shift and incapacity of NK cells in the tumor microenvironment is essential for improving antitumor effects. dl-tetrahydropalmatine (dl-THP), one of the active alkaloids of Chinese herb Corydalis Rhizoma, has been proven to possess antitumor activity. However, whether dl-THP acts on NK cells to enhance antitumor activity remains unknown. In this study, we found that the proportion of blood CD56dimCD16+ NK cells was decreased while the proportion of CD56brightCD16- NK cells was increased when the cells were cultured in conditional medium (CM, medium from the human choriocarcinoma cell lines JEG-3). dl-THP could alter the varied proportion of CD56dimCD16+ NK cells and CD56brightCD16- NK cells in CM respectively. Importantly, the expression level of NKp44 on CD56dimCD16+ NK cells was dramatically reduced when the cells were cultured in CM, which could also be reversed by dl-THP. Furthermore, dl-THP increased the decreased NK-cell cytotoxicity when cells were cultured in CM. In summary, our study demonstrated that dl-THP could recover the decreased NKp44 expression level on CD56dimCD16+ NK cells and restore the cytotoxicity of NK cells in tumor microenvironment.

Ulcerative colitis (UC) is a refractory and recurring inflammatory bowel disease (IBD). Monocytes and macrophages are major components of the mononuclear phagocyte system (MPS), and the balance between inflammatory monocytes and small peritoneal macrophages plays important roles in UC. However, the mechanisms governing the balance between inflammatory monocytes and small peritoneal macrophages in UC need to be clarified further. Here, we found that the expression levels of CD226 on different subsets of monocytes/macrophages are varied in UC mice. The expression levels of CD226 on patrolling monocytes (pMos) and small peritoneal macrophages (SPMs) were markedly increased, while the expression levels of CD226 on inflammatory monocytes (iMos) were decreased in UC mice. Significantly, the percentage of iMos was enhanced while the percentage of SPMs were decreased in CD226 knockout UC mice compared with that in wildtype UC mice. Moreover, CD226 deficiency suppressed the migration capacity of macrophages. Therefore, our data suggest that CD226 plays critical roles in regulating the function and balance of monocytes/macrophages in mouse UC and targeting CD226 in MPS may be developed as a potent therapy for UC.