Research Group Susanne Gabrielsson
The role of exosomes in the immune system and how to use them in therapy and as disease biomarkers.
Exosomes are 30-100 nm sized extracellular vesicles, released from most cells in the body, including dendritic cells, macrophages, T and B cells, epithelial cells, and tumor cells. They work as messengers between cells and can deliver cargo such as enzymes, mRNA, microRNA and immunoregulatory proteins. During the last years, results from us and others have revealed that exosomes exist in most body fluids. We have made the discovery of exosomes in bronchoalveolar lavage (BAL) fluid and also in breast milk. We have reported that BAL exosomes from patients with both asthma and sarcoidosis are pro-inflammatory and might contribute to pathogenesis of lung diseases. In contrast, milk exosomes inhibit cytokine production, mediated by T regulatory cells, suggesting that milk exosomes might protect the child from allergies.
The mechanism of action of exosomes in vivo is not fully understood, but they seem to have functions similar to those of whole cells. Exosomes from antigen presenting cells contain both MHC I and II, as well as co-stimulatory molecules, and can stimulate T cells in vitro. This led to the idea that exosomes generated in vitro might be used for cancer therapy. Indeed, dendritic cell derived exosomes constitute novel therapeutic vehicles, but still mechanisms for activation are unclear and should be optimized. We have shown that exosomes function as a Th1-inducing adjuvant through a B cell dependent mechanism and that the effect of an NKT cell ligand is synergized when bound to exosomes, leading to tumour destruction. This raises the hopes that exosomes could be used as cancer treatment in the future.
- To elucidate the molecular mechanisms behind exosome induced immune stimulation.
- To understand the role of exosomes in inflammatory diseases such as Asthma, COPD and Sarcoidosis.
- To potentiate immunogenicity of exosomes by exosome engineering.
We hope to find more efficient exosome-based therapies for cancer, autoimmunity and allergy. This work might also lead to improved methods to detect cancer and lung diseases.