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

Ashwin Jainarayanan; Ranjeet Singh Mahla; Jesusa Capera; Mirudula Elanchezhian; Dhanu Gupta; Nithishwer Mouroug Anand; Tom R Thomas; Daniel Beckers; Alexander Leithner; Sooraj R. Achar; Salvatore Valvo; Mariana Conceição; Elke Kurz; Abhinandan Devaprasad; Sakina Amin; G. Berridge; Svenja Hester; Román Fischer; Pablo F. Céspedes; Lynn B. Dustin; Matthew J. A. Wood; Michael Loran Dustin

doi:10.1101/2024.10.15.618584

ImmunologybioRxivOct 15, 2024

Preprint

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

Ashwin Jainarayanan iD, Ranjeet Singh Mahla iD, Jesusa Capera iD, Mirudula Elanchezhian iD, Dhanu Gupta iD, Nithishwer Mouroug Anand, Tom R Thomas iD, Daniel Beckers iD, Alexander Leithner iD, Sooraj R. Achar iD, Salvatore Valvo iD, Mariana Conceição iD, Elke Kurz iD, Abhinandan Devaprasad, Sakina Amin iD, G. Berridge, Svenja Hester iD, Román Fischer iD, Pablo F. Céspedes iD, Lynn B. Dustin iD, Matthew J. A. Wood iD, Michael Loran Dustin iD

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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.