Control of MAIT cell functions by cytokines in health and disease

Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that express a semi-invariant T cell receptor (TCR). These cells predominantly reside in tissues, such as the liver, lung, skin and the gastrointestinal tract. MAIT cells can be activated via their TCR that recognizes riboflavin metabolites presented by the MHC class I-related protein 1 (MR1). These cells can also be activated in a TCR-independent manner by cytokines, in particular IL-12 and IL-18, but also by type I interferons, IL-7, IL-15 and IL-23, underlining their innate-like characteristics. MAIT cells have important functions in antibacterial and viral immunity but also in tissue repair and homeostasis. Recent studies highlighted the plasticity of MAIT cells in response to cytokines, suggesting an important role of the cytokine milieu in modulating MAIT cell functions. Here, we discuss how cytokines control MAIT cell functions in various contexts.

Keywords: Cytokines; MAIT cell activation; MAIT cells; cell plasticity; infectious diseases; inflammatory diseases; interleukins; tissue repair.

Figure 1

Control of MAIT cell functions by cytokines. Summary of the effects of cytokines on MAIT cell functions. MAIT cells can be activated in the absence of a TCR stimulus (left panel) by cytokines such as IL-7, IL-18, IL-15, type I interferons or the combination of IL-12+IL-18. MAIT cells exhibit various responses to cytokines as they can secrete pro-inflammatory cytokines (e.g. IFN-γ), cytotoxic mediators or adopt a tissue repair program. The cytokine milieu can also influence MAIT cell functions in the presence of a TCR stimulus (right panel). MAIT cells can adopt distinct functional and transcriptional profiles in response to different cytokines, highlighting their plasticity.