A resource for extracellular vesicles from activated CD4 T cells that relay pro-inflammatory signals

Jainarayanan, A. K.; Mahla, R. S.; Capera, J.; ELANCHEZHIAN, M.; Gupta, D.; Anand, N. M.; Thomas, T.; Beckers, D.; Leithner, A.; Achar, S. R.; Valvo, S.; Conceicao, M.; Kurz, E.; Devaprasad, A.; Amin, S.; Berridge, G.; Hester, S.; Fischer, R.; Cespedes, P. F.; Dustin, L. B.; Wood, M. J. A.; Dustin, M. L.

doi:10.1101/2024.10.15.618584

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bioRxiv · 10.1101/2024.10.15.618584

A resource for extracellular vesicles from activated CD4 T cells that relay pro-inflammatory signals

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Abstract

CD4 T helper cells (TH cells) play a vital role in coordinating and amplifying the immune response to specific pathogens. They constitutively produce different kinds of extracellular vesicles (EVs), which mediate cell-to cell communication and play diverse roles in immune regulation and inflammatory processes. Here we provide a resource documenting the composition of activated TH cell EVs and demonstrating their ability to instigate pro-inflammatory response in antigen-presenting cells (APCs). EVs were characterized by lipidomics, proteomics, and NanoFCM. The activated TH cells derived EVs (act-EVs) were found to be enriched in TH cell-specific proteins, transmembrane and cytosolic EV marker proteins, and HLA proteins relative to resting CD4 T cells EVs (rest-EVs). The pro-inflammatory effect of act-EVs vs rest-EVs on donor matched APCs were characterized by chemokine and cytokine profiling and flow cytometry analysis. There was no discernible contrast in endotoxin levels between act-EVs and rest-EVs. Functional distinctions were seen to arise from variations in the content and composition of these EVs. Moreover, we validated our findings with an in-vivo investigation in mice, demonstrating the recruitment of monocytes, dendritic cells (DCs), neutrophils, and NK cells in the spleen, accompanied by the release of pro-inflammatory cytokines in the serum after administering act-EVs. In summary, this study sheds light on the role of TH cell released EVs in modulating the immune response during pro-inflammatory responses and this resource provides a foundation for development of novel therapeutics on EV based scaffolds.

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Jainarayanan, A. K., Mahla, R. S., Capera, J., ELANCHEZHIAN, M., Gupta, D., Anand, N. M., Thomas, T., Beckers, D., Leithner, A., Achar, S. R., Valvo, S., Conceicao, M., Kurz, E., Devaprasad, A., Amin, S., Berridge, G., Hester, S., Fischer, R., Cespedes, P. F., Dustin, L. B., Wood, M. J. A., Dustin, M. L.. 2024-10-18. A resource for extracellular vesicles from activated CD4 T cells that relay pro-inflammatory signals. https://doi.org/10.1101/2024.10.15.618584

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