The Mechanism Of Tfh Cell Dysfunction Induced By Exosomal MiR-155 Involved In The Microenvironmental Immunodissonance In CLL

Objectives:To investigate the role of chronic lymphocytic leukemia(CLL)exosomes carrying miR155 in immune disorders of the tumor microenvironment and the mechanisms that further promote tumor progression.Methods:1.CLL cell line MEC-1 exosomes were extracted and co-cultured with normal donor T cells,and the Tfh subpopulation ratio and miR155 expression with its downstream genes were detected by flow cytometry,and then the exosome-induced T cells were co-cultured with CLL primary cells and cell lines to detect tumor cell proliferation.2.After treatment of CLL cell line MEC-1 with vitamin D,exosomes were extracted and the above experiments were repeated.Results:1.Flow-through results showed that Tfh ratio increased,miR155 expression was elevated and fosl2 expression was down-regulated after co-culture of CLL-derived exosomes with normal donor T cells,and the exosome-induced T cells were able to significantly promote the proliferation of CLL cells.Further studies revealed that IL-21,IL-4,and CXCL13 secretion were increased in Tfh cells after exosome induction.2.The pro-Tfh differentiation and IL-21,IL-4,and CXCL13 secretion capacity of exosomes after treatment with vitamin D were reduced,and the pro-tumor proliferation capacity of T cells after exosome induction by vitamin D treatment was decreased.Conclusion:1.CLL cells can act on normal T cells by secreting exosomes carrying miR155 to induce Tfh differentiation,and Tfh cells induced by CLL-derived exosomes can significantly promote CLL proliferation.2.miR155 in CLL-derived exosomes induced Tfh differentiation by inhibiting fosl2 expression in T cells,and Tfh cells induced by CLL-derived exosomes secreted IL-21,IL-4 and CXCL13 to promote CLL proliferation.3.Vitamin D can effectively reverse the effect of CLL-derived exosomes induced Tfh differentiation and thus inhibit CLL proliferation.