Intestinal microbes influence development of thymic lymphocytes in early life
| Autor: | Bobby J. Cherayil, Chithirachelvi Vasudevan, Vladimir Yeliseyev, Nitya Jain, Stefan Halvorsen, Samira Ibrahim, Shaniah Prosper, Slim Sassi, Smriti Verma, Maria Ennamorati, Kara Clerkin, Joseph A. Gardecki, Brian Seed, Lynn Bry, Caryn Porter, Margot Kim, Guillermo J. Tearney |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Colon T cell Cell Thymus Gland Gut flora Bacteroides fragilis Mice 03 medical and health sciences 0302 clinical medicine Antigen Precursor cell medicine Animals Humans Promyelocytic Leukemia Zinc Finger Protein Lymphocytes Multidisciplinary Bacteria biology Cell Differentiation Biological Sciences Colitis biology.organism_classification Gastrointestinal Microbiome Mice Inbred C57BL 030104 developmental biology Lymphatic system medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Homeostasis |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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