GUT MICROBIOTA IS A MODULATOR OF INTRAEPITHELIAL LYMPHOCYTE NUMBERS AND PHENOTYPE IN THE SMALL INTESTINE

Intraepithelial lymphocytes (IELs), αβTCR and γδTCR, play a critical role in mucosal barrier maintenance and as revealed by some gnotobiotic studies, their populations are modulated by the presence of the microbiota. Previous research has demonstrated that αβTCR IELs are responsible for infection-associated damage in the gut and are hypothesized to contribute to villous atrophy in celiac disease (CD). Our aim was to determine whether microbiota from CD patients, characterized by dysbiosis, influenced IEL populations in the small intestine (SI). We thus transferred human stools from CD or healthy individuals into germ-free (GF) C57BL/6 mice. Stool from one out of three CD donors (CD3) increased IELs within the SI villi tips, and increased proportions of αβTCR IELs. 16S rDNA sequencing of SI contents revealed a higher composition of Proteobacteria, specifically Parasutterella, in mice colonized with CD3 microbiota. Further investigation demonstrated that IEL responses to colonization were dependent on MyD88 and TICAM1 signaling, suggesting that the composition of gut microbiota can alter IEL numbers and phenotype in the SI through a MyD88/TICAM1 pathway. This mechanism may play a pathogenic role in diseases where IEL proliferation and activation is central to disease development such as celiac disease, food allergy or IBD.