|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.; Hackermüller, J.; von Bergen, M.|
|Journal||Frontiers in Immunology|
|Page From||art. 616967|
|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||https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=23751|
|Schubert, K., Karkossa, I., Schor, J., Engelmann, B., Steinheuer, L.M., Bruns, T., Rolle-Kampczyk, U., Hackermüller, 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