Publication Details

Category Text Publication
Reference Category Journals
DOI 10.3389/fimmu.2021.616967
Licence creative commons licence
Title (Primary) A multi-omics analysis of mucosal-associated-invariant T cells reveals key drivers of distinct modes of activation
Author Schubert, K.; Karkossa, I.; Schor, J.; Engelmann, B.; Steinheuer, L.M.; Bruns, T.; Rolle-Kampczyk, U.; Hackerm├╝ller, J. ORCID logo ; von Bergen, M.
Source Titel Frontiers in Immunology
Year 2021
Department MOLSYB
Volume 12
Page From art. 616967
Language englisch
Topic T9 Healthy Planet
Keywords MAIT cell, Multi-omics analysis, TCR-dependent, TCR-independent, activation, Key driver analysis
Abstract The function of mucosal-associated invariant T (MAIT) highly depends on the mode of activation, either by recognition of bacterial metabolites via their T cell receptor (TCR) or in a TCR-independent manner via cytokines. The underlying molecular mechanisms are not entirely understood. To define the activation of MAIT cells on the molecular level, we applied a multi-omics approach with untargeted transcriptomics, proteomics and metabolomics.
Transcriptomic analysis of E.coli- and TCR-activated MAIT cells showed a distinct transcriptional reprogramming, including altered pathways, transcription factors and effector molecules. We validated the consequences of this reprogramming on the phenotype by proteomics and metabolomics. Thus, and to distinguish between TCR-dependent and -independent activation, MAIT cells were stimulated with IL12/IL18, anti-CD3/CD28 or both. Only a combination of both led to full activation of MAIT cells, comparable to activation by E.coli. Using an integrated network-based approach, we identified key drivers of the distinct modes of activation, including cytokines and transcription factors, as well as negative feedback regulators like TWIST1 or LAG3.
Taken together, we present novel insights into the biological function of MAIT cells, which may represent a basis for therapeutic approaches to target MAIT cells in pathological conditions.
Persistent UFZ Identifier
Schubert, K., Karkossa, I., Schor, J., Engelmann, B., Steinheuer, L.M., Bruns, T., Rolle-Kampczyk, U., Hackerm├╝ller, J., von Bergen, M. (2021):
A multi-omics analysis of mucosal-associated-invariant T cells reveals key drivers of distinct modes of activation
Front. Immunol. 12 , art. 616967 10.3389/fimmu.2021.616967