Immunity is a complex and sophisticated network that orchestrates various subsets of immune cells. Both innate and adaptive immunity interact to protect the body against threats from foreign antigens, which are mainly associated with microbial pathogens. However, an excess immune response or activation of lymphocytes by self-antigens causes hypersensitivity or autoimmune disease that destroys specific tissues or cells. Therefore, appropriate immunotherapy is needed according to diseases. In this thesis, mechanisms of immune modulation by two exogenous factors: natural compound and probiotics and one endogenous factor: epigenetic modulator are studied. In first research, there was defined the molecular mechanism of how dictabretol A has anti-lymphoproliferative effects and demonstrated the therapeutic efficacy of dictabretol A in a rheumatoid arthritis model. Dictabretol A specifically blocked the cell cycle transition from the G1 phase to the S phase by inhibiting Erk-dependent signaling and may be a candidate novel therapeutic agent to treat chronic inflammatory disease. And in second study, the immunomodulatory roles of L.plantarum strains administration were evaluated in a murine model of BP allergy, a Th2 immune disorder. Through these findings, some strains of probiotics are powerful inducers of the Th1 immune response, and, so, can be used as therapeutic options for BP-induced allergic rhinitis. Finally, last study demonstrated epigenetic modulator Phc2-regulates M2 macrophage polarization through the repression of Mafb gene expression. These finding may offer new therapeutic strategies to regulates microbial infection or tumor microenvironment.