Therapeutic potential of Inonotus obliquus polysaccharide-induced tolerogenic bone marrow-derived dendritic cells via regulation of CD4+ T cell differentiation in a colitis mouse model

Abstract

Over-proliferation, activation, or aberrant CD4⁺ T cell differentiation causes various immune-related diseases. DCs are significant professional APCs that regulate the differentiation of CD4⁺ T cells to participate in an inflammatory response. IOP is an edible fungal polysaccharide with immunoregulatory and anti-inflammatory bioactivities, however, the cellular mechanisms by which they regulate the immune system to exert their anti-inflammatory effects remain unclear. The present study aimed to investigate the effects of IOP on the regulation of CD4⁺ T cell differentiation and the correlative mechanisms related to DCs. IOP did not regulate the proliferation and activation of CD4⁺ T cells. However, it inhibited the differentiation of Th1 and Th17 cells and promoted the differentiation of Treg cells. IOP maintained the immature phenotype of BMDCs, which induces immune tolerance and promotes the differentiation of CD4⁺ T cells into Treg cells. Transfusion of IOP_L-BMDC into colitis mice markedly alleviated colitis-associated inflammation and maintained the colon's integrity. IOP_L-BMDCs inhibited the differentiation of CD4⁺ T cells into inflammatory effective Th1 cells in the spleen and MLN while promoting their differentiation into immune-tolerant, anti-inflammatory Treg cells. In conclusion, this research demonstrated that IOP strongly regulates the polarization of CD4⁺ T cells to Treg subsets with inflammatory suppressive effects by inducing immature tolerant DCs, which provides strategic evidence for the therapeutic application of IOP in colitis, and IOP-induced tolerant DCs provide a new therapeutic approach to the development of a DC vaccine for colitis.

Keywords: CD4(+) T cells; Colitis; IOP; Immature tolerant DCs.