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Journal of Immunology Research
Volume 2014 (2014), Article ID 279736, 11 pages
http://dx.doi.org/10.1155/2014/279736
Research Article

Appropriate Development of the Liver Treg Compartment Is Modulated by the Microbiota and Requires TGF-β and MyD88

1The Geisel School of Medicine at Dartmouth, Department of Microbiology and Immunology, DHMC, One Medical Center Drive, Lebanon, NH 03756, USA
2The Geisel School of Medicine at Dartmouth, Department of Pathology, DHMC, One Medical Center Drive, Lebanon, NH 03756, USA

Received 3 May 2014; Accepted 30 June 2014; Published 7 August 2014

Academic Editor: David Bernardo Ordiz

Copyright © 2014 Ann Maria et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 FoxP3EGFP 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+ cells. To assess roles for TGF-, 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 FoxP3+ 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- 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- and MyD88, but not TLR2.