Immunostimulatory activity of murine keratinocyte-derived exosomes.

Keratinocytes are able to influence cutaneous immunity by taking part in innate as well as in adaptive immune processes. To fulfill this task, the production of soluble factors has a key role. Exosomes, small membrane vesicles of endocytic origin and secreted by a variety of cells, may modify immune responses. However, little is known about the immunological function of keratinocyte-derived exosomes. To address this question, the murine keratinocyte cell line MPEK was cultured in vitro, and the production of exosomes has been demonstrated. These exosomes were internalized by bone marrow-derived dendritic cells (BMDC), where they induced production of high amounts of IL-6, IL-10, and IL-12 as well as increased surface expression of CD40. When MPEK were incubated with antigen, they transferred it to their exosomes. However, antigen loaded exosomes failed to induce an antigen specific T cell response directly or via BMDC. When environmental conditions, mimicked by cytokine cocktails characteristic for two of the most common chronic inflammatory skin disorders, atopic dermatitis or psoriasis, were modulated, a profound impact on the molecular repertoire of exosomes was found. The specifically altered components comprised virtually all functional fields. Even though MPEK derived exosomes did not elicit an antigen-specific T cell response, they were clearly able to influence BMDC function and phenotype. Further, interleukins and IFNγ markedly influenced the molecular exosome composition. Together, these findings suggest an immunomodulatory function for MPEK-derived exosomes and a crucial effect of environmental conditions on exosome composition end presumably even function.