Poster Presentation CD1-MR1 2024

MAIT cells exert tissue repair function at steady state in tissues (#110)

Anne-laure Le Gac 1 , Aurélie Darbois 1 , Anastasia du Halgouet 1 , Hélène Bugaut 1 , Martin Mestdagh 1 , Olivier Lantz 1 , Marion Salou 1
  1. Institut Curie, Paris, FRANCE, France

MAIT cells are present in mucosal tissues, in which they exert various functions depending on the context, from anti-bacterial effect to tissue repair. We recently showed that the transcriptome of skin MAIT cells was not modified during wound healing, suggesting that the repair program was preexisting. Whether this program exists in other organs at steady state is unknown. Comparison of single cell transcriptomic datasets of thymus, mediastinal lymph node (LN) and lung MAIT cells evidenced a tissue repair program in the lung at steady state. While obtaining a single cell suspension from thymus and LN only requires mechanical tissue disruption, other organs such as the lung or the skin undergo several digestion steps at 37°C. Such protocol increases the stress response of the cells and biases the transcriptome analysis. To examine the impact of diverse digestion protocols on transcriptomic analysis, we generated scRNAseq datasets of LN MAIT cells digested or not following the protocols used for skin and lung. Comparison of these datasets defined a list of genes which can be regressed out in the bioinformatic pipeline to mitigate the effects of the digestion processes when needed. Thus, we confirmed that lung MAIT cells express tissue repair molecules at steady state, despite no sign of TCR triggering, as shown by studying a Nr4a1-GFP reporter mouse. Accordingly, we recently published that thymic MAIT cells stimulated by IL-18 expressed similar levels of amphiregulin, an epidermal growth factor, as compared to 5-OP-RU stimulated thymic MAIT cells, suggesting that TCR triggering alone is not responsible for acquisition of repair functions. Altogether these data suggest that more studies are needed to fully uncover how MAIT cell acquire and mediate their tissue repair functions.