Intestinal microbes influence development of thymic lymphocytes in early life

Proc Natl Acad Sci U S A. 2020 Feb 4;117(5):2570-2578. doi: 10.1073/pnas.1915047117. Epub 2020 Jan 21.


The thymus generates cells of the T cell lineage that seed the lymphatic and blood systems. Transcription factor regulatory networks control the lineage programming and maturation of thymic precursor cells. Whether extrathymic antigenic events, such as the microbial colonization of the mucosal tract also shape the thymic T cell repertoire is unclear. We show here that intestinal microbes influence the thymic homeostasis of PLZF-expressing cells in early life. Impaired thymic development of PLZF+ innate lymphocytes in germ-free (GF) neonatal mice is restored by colonization with a human commensal, Bacteroides fragilis, but not with a polysaccharide A (PSA) deficient isogenic strain. Plasmacytoid dendritic cells influenced by microbes migrate from the colon to the thymus in early life to regulate PLZF+ cell homeostasis. Importantly, perturbations in thymic PLZF+ cells brought about by alterations in early gut microbiota persist into adulthood and are associated with increased susceptibility to experimental colitis. Our studies identify a pathway of communication between intestinal microbes and thymic lymphocytes in the neonatal period that can modulate host susceptibility to immune-mediated diseases later in life.

Keywords: early-life immunity; mucosal immunity; thymic lymphocyte development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Bacteroides fragilis / physiology
  • Cell Differentiation
  • Colitis / genetics
  • Colitis / immunology
  • Colitis / microbiology
  • Colon / microbiology
  • Gastrointestinal Microbiome*
  • Humans
  • Lymphocytes / cytology
  • Lymphocytes / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Promyelocytic Leukemia Zinc Finger Protein / genetics
  • Promyelocytic Leukemia Zinc Finger Protein / immunology
  • Thymus Gland / cytology
  • Thymus Gland / growth & development*
  • Thymus Gland / immunology


  • Promyelocytic Leukemia Zinc Finger Protein
  • Zbtb16 protein, mouse