학술논문
Appropriate Development of the Liver Treg Compartment Is Modulated by the Microbiota and Requires TGF-β and MyD88.
Document Type
Article
Source
Subject
*PARTURITION
*TRANSCRIPTION factors
*TRANSFORMING growth factors-beta
*TOLL-like receptors
*GRAM-positive bacteria
*DENDRITIC cells
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Language
ISSN
2314-8861
Abstract
Neither the early postnatal development of the liver Treg compartment nor the factors that regulate its development has been characterized. We compared the early developmental patterns of Treg cell accumulation in murine liver, thymus, and spleen. A FoxP3[sup EGFP][reporter mouse was employed to identify Treg cells. Mononuclear cells were isolated from organs postnatally, stained for CD4, and examined by flow cytometry to enumerate FoxP3[sup +][D4[sup hi][cells. To assess roles for TGF-β1, MyD88, and TLR2, gene-specific knockout pups were generated from heterozygous breeders. To test the role of commensal bacteria, pregnant dams were administered antibiotics during gestation and after parturition. The pattern of appearance of Treg cells differed in liver, spleen, and thymus. Notably, at 1-2 weeks, the frequency of CD4[sup hi][FoxP3[sup +][T cells in liver exceeded that in spleen by 1.5- to 2-fold. The relative increase in liver Treg frequency was transient and was dependent upon TGF-β1 and MyD88, but not TLR2, and was abrogated by antibiotic treatment. A relative increase in liver Treg frequency occurs approximately 1-2 weeks after parturition that appears to be driven by colonization of the intestine with commensal bacteria and is mediated by a pathway that requires TGF-β1 and MyD88, but not TLR2. [ABSTRACT FROM AUTHOR]