Figure 8.

Hypothetical model of the possible mechanisms used by the MVs-ICAM-1^high in the immunoregulation of dendritic cells and T lymphocytes. The generation of an inflammatory environment by mature DCs capable of activating T lymphocytes (A) would increase the immunoregulatory capacity of BM-MSCs and stimulate the release of MVs-ICAM-1^high, which could travel through the bloodstream (B) and contact target cells, such as dendritic cells and T lymphocytes, through ICAM-1. These structures could contribute to the maintenance of DCs in an immature state, unable to adequately stimulate T lymphocytes (C). Likewise, MVs-ICAM-1^high could bind to LFA-1 in T lymphocytes, decreasing their ability to form a stable immune synapse, as well as the interaction between them (D). Besides, the direct interaction of MVs-ICAM-1^high with DCs or T lymphocytes would also favor the paracrine action of other immunosuppressive molecules transported by these structures. Due to the above, it is possible that MVs replicate the immunosuppression exerted by the whole cell, resulting in the generation of an anti-inflammatory environment in which the proliferation of T lymphocytes and the differentiation of Th1 and Th17 cells decrease, while increasing the differentiation of regulatory T cells (E). Dotted arrows and dotted line text boxes indicate the hypothetical mechanisms that MVs-ICAM-1^high could use in the immunoregulation of dendritic cells and T lymphocytes.