Host immune system and microenvironment

The term "Host immune cells and tissues via paracrine factors, cell-cell contact, and extracellular vesicles" describes a complex physiological interface rather than a single molecular target. It refers to the collective biological system—comprising immune cell subsets like T cells, macrophages, and dendritic cells, as well as the surrounding tissue architecture—that responds to therapeutic interventions such as Mesenchymal Stem Cells (MSCs) or extracellular vesicle (EV) therapies (Galipeau & Sensébé, 2018). These therapies exert their effects through three primary modalities: the secretion of soluble paracrine mediators (e.g., cytokines and growth factors), direct physical cell-cell contact (e.g., PD-L1/PD-1 interactions), and the release of EVs that transport proteins and nucleic acids to recipient cells (Wiklander et al., 2019). This multi-faceted interaction is critical for achieving immunomodulation and promoting tissue repair in conditions such as graft-versus-host disease, Crohn's disease, and various inflammatory disorders (Pittenger et al., 2019). Because it involves a systemic network of interactions, it is often characterized as a "systemic target" or a therapeutic interface in regenerative medicine and immunotherapy (Fan et al., 2020). Understanding this interface requires evaluating the holistic change in the host microenvironment rather than the inhibition or activation of a single enzyme or receptor.

Other names

Host immune cells and tissuesImmune microenvironmentParacrine signaling networkExtracellular vesicle-mediated communication interface

Modulation of the host immune environment through the secretion of soluble paracrine factors, direct membrane-bound protein interactions (cell-cell contact), and the horizontal transfer of bioactive molecules (miRNA, proteins) via extracellular vesicles.