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The steroid and xenobiotic receptor negatively regulates B-1 cell development in the fetal liver

Stephanie C Casey1, Bruce Blumberg

  • 1Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA.

Molecular Endocrinology (Baltimore, Md.)
|April 13, 2012
PubMed

Insights

The steroid and xenobiotic receptor (SXR) plays a novel role in fetal liver development. SXR activation during development impacts B-1 cell populations, suggesting a role in immune system modulation.

Area of Science:

  • Immunology
  • Endocrinology
  • Developmental Biology

Background:

  • The steroid and xenobiotic receptor (SXR), also known as pregnane X receptor (PXR), is a nuclear hormone receptor involved in drug and xenobiotic metabolism.
  • SXR is highly expressed in the liver and intestine, with less understood roles in other tissues.
  • Previous studies showed SXR deficiency leads to elevated NF-κB activity, NF-κB target gene overexpression, and B-1 lymphocyte lymphoma in mice.

Purpose of the Study:

  • To investigate the role of SXR in fetal liver development and hematopoiesis.
  • To explore the impact of SXR on B-1 progenitor cell populations.
  • To determine if SXR influences the immune system during embryonic development.

Main Methods:

  • Analysis of fetal liver tissues from SXR(-/-) mice and wild-type mice.
  • Assessment of NF-κB target gene expression.
  • Flow cytometry to quantify B-1 progenitor cells.
  • In utero SXR activation studies in wild-type mice.

Main Results:

  • SXR(-/-) fetal livers exhibited elevated NF-κB target gene expression and a higher percentage of B-1 progenitor cells.
  • In utero SXR activation in wild-type mice reduced B-1 progenitor populations in embryonic livers.
  • Prenatal SXR activation led to smaller B-1 cell compartments in adult animals.

Conclusions:

  • SXR plays a significant role in modulating developmental hematopoiesis within the fetal liver.
  • SXR activation during development can permanently alter the immune system.
  • These findings establish SXR as a novel modulator of B-1 cell precursor generation and support its function as a tumor suppressor in B-1 lymphocytes.

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