Intestinal microbes influence development of thymic lymphocytes in early life
Maria Ennamorati, Chithirachelvi Vasudevan, Kara Clerkin, Stefan Halvorsen, Smriti Verma, Samira Ibrahim, Shaniah Prosper, Caryn Porter, Vladimir Yeliseyev, Margot Kim, Joseph A. Gardecki, Slim Sassi, Guillermo J. Tearney, Bobby J. Cherayil, Lynn Bry, Brian Seed, Nitya Jain
Abstract
Significance The burgeoning intestinal microbiota pose a unique challenge to the developing immune system of the newborn. Extensive crosstalk between mucosal immune cells and microbes is necessary to establish healthy microbial communities and promote the development of productive mucosal immunity. However, it is yet unknown whether intestinal microbes also influence the development of lymphocytes themselves in the thymus. Here, we report that thymic distribution of transcription factor PLZF-expressing innate lymphocytes is regulated by intestinal microbes in early life. Migratory plasmacytoid dendritic cells are one conveyor of microbial information to developing thymic cells and perturbation of this entero-thymic communication in early life impacts disease susceptibility in adulthood. Our data highlight a novel regulation of thymic lymphocyte development by early-life microbiota.