JAX CRC investigators Derya Unutmaz and Julia Oh have written a Science Immunology perspective review on two exciting articles that have just been published in Science, which show very close interactions between an immune cell subtype called mucosal-associated invariant T (MAIT) cells and the microbiota. MAIT cells are a special type of T cell that are stimulated by vitamin B2 derivatives that have been produced by bacteria, and it is thought that MAIT cells control the immune response to bacterial, fungal and even some viral infections.
The first article, by M.G. Constantinides et al., shows that commensal, or friendly, bacteria control the development of MAIT cells in the thymus, and the second, by F. Legoux et al., shows that these commensal bacteria also control the expansion of MAIT cells into the mucosal tissues and specifically play a role in the skin and in wound healing. Overall, these two studies combined illustrate how in mice, development and expansion of MAIT cells are tightly linked to exposure to commensal microbiota during a crucial early-life developmental stage. The studies further illustrate the additional complexity within the MAIT cells, and identify a subset with unique function in tissue repair.
In humans, it’s not yet known how the exposure to microbiota in early-life and later in life contribute to MAIT maturation and expansion. Important questions remain as well about how MAIT cells are able to discriminate pathogenic species of microbes from commensal ones. Why are they not chronically activated, since they’re in constant close proximity to microbes? It’s thought that MAIT cells can tune their output based on environmental signals, including the vitamin B2 derivatives produced by bacteria, plus other signals.
MAIT cell numbers can vary by up to 40-fold across individuals, and in the accompanying perspective article, Julia Oh and Derya Unutmaz discuss that we need to understand this dynamic range in MAIT cells between individuals. We also need to understand the precise role that MAIT cells play in infections, cancer, and other chronic infections. As such, these two new articles provide an important framework to future studies to understand the relationship between MAIT cells and their involvement in chronic diseases.
Unutmaz is also interested in what role MAIT cells may play in ME/CFS, a chronic condition with known differences between healthy controls and ME/CFS patients in their microbiota and immune systems. Towards that goal, Oh and Unutmaz mention that the “personalized MAIT cell frequency and function is disrupted during aging, certain chronic infections such as HIV, and other chronic diseases. Whether manipulating the microbiota can reconstitute such personalized functionality warrants further investigation.”