A path forward to improving the specificity of immunotherapies

Barber, Brittany; Mair, Florian; Prlic, Martin

doi:10.1002/ctm2.1051

Cited by 1 publication

(1 citation statement)

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“…These combinatorial signal events further enhance the complexity, but recent advances in the development of data analysis tools have started to allow us to predict human cell–cell signaling interactions 127 . This enables us to discover new biology 122 and potential therapeutic interventions, 128 and ask more pertinent questions in follow‐up ex vivo experiments with human cells. In the future, our ability to predict and interpret more complex (combinatorial) signaling events will further improve.…”

Section: Summary and Outlook For Improving Our Understanding Of Mait ...mentioning

confidence: 99%

Signals that control MAIT cell function in healthy and inflamed human tissues

Konecny,

Huang,

Setty

et al. 2024

Immunological Reviews

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SummaryMucosal‐associated invariant T (MAIT) cells have a semi‐invariant T‐cell receptor that allows recognition of antigen in the context of the MHC class I‐related (MR1) protein. Metabolic intermediates of the riboflavin synthesis pathway have been identified as MR1‐restricted antigens with agonist properties. As riboflavin synthesis occurs in many bacterial species, but not human cells, it has been proposed that the main purpose of MAIT cells is antibacterial surveillance and protection. The majority of human MAIT cells secrete interferon‐gamma (IFNg) upon activation, while some MAIT cells in tissues can also express IL‐17. Given that MAIT cells are present in human barrier tissues colonized by a microbiome, MAIT cells must somehow be able to distinguish colonization from infection to ensure effector functions are only elicited when necessary. Importantly, MAIT cells have additional functional properties, including the potential to contribute to restoring tissue homeostasis by expression of CTLA‐4 and secretion of the cytokine IL‐22. A recent study provided compelling data indicating that the range of human MAIT cell functional properties is explained by plasticity rather than distinct lineages. This further underscores the necessity to better understand how different signals regulate MAIT cell function. In this review, we highlight what is known in regards to activating and inhibitory signals for MAIT cells with a specific focus on signals relevant to healthy and inflamed tissues. We consider the quantity, quality, and the temporal order of these signals on MAIT cell function and discuss the current limitations of computational tools to extrapolate which signals are received by MAIT cells in human tissues. Using lessons learned from conventional CD8 T cells, we also discuss how TCR signals may integrate with cytokine signals in MAIT cells to elicit distinct functional states.

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Section: Summary and Outlook For Improving Our Understanding Of Mait ...mentioning

confidence: 99%