An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells

Nat Immunol. 2004 Jan;5(1):64-73. doi: 10.1038/ni1022. Epub 2003 Dec 21.

Abstract

Lymphoid tissue inducer (LTi) cells are associated with early development of lymph nodes and Peyer's patches. We show here that during fetal life the nuclear hormone receptor RORgamma(t) is expressed exclusively in and is required for the generation of LTi cells. RORgamma(t+) LTi cells provide essential factors, among which lymphotoxin-alpha1beta2 is necessary but not sufficient for activation of the mesenchyma in lymph node and Peyer's patch anlagen. This early LTi cell-mediated activation of lymph node and Peyer's patch mesenchyma forms the necessary platform for the subsequent development of mature lymphoid tissues.

MeSH terms

  • Animals
  • Embryonic and Fetal Development / genetics
  • Embryonic and Fetal Development / immunology
  • Embryonic and Fetal Development / physiology
  • Female
  • Flow Cytometry
  • Green Fluorescent Proteins
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / immunology
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Lymphoid Tissue / embryology*
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / physiology
  • Lymphotoxin-alpha / immunology
  • Male
  • Mice
  • Mice, Knockout
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Organogenesis / genetics
  • Organogenesis / immunology
  • Organogenesis / physiology*
  • Receptors, Interleukin-7 / genetics
  • Receptors, Interleukin-7 / immunology
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / immunology
  • Receptors, Retinoic Acid / physiology*
  • Receptors, Thyroid Hormone / genetics
  • Receptors, Thyroid Hormone / immunology
  • Receptors, Thyroid Hormone / physiology*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / immunology

Substances

  • Luminescent Proteins
  • Lymphotoxin-alpha
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Receptors, Interleukin-7
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • Vascular Cell Adhesion Molecule-1
  • interleukin-7 receptor, alpha chain
  • Intercellular Adhesion Molecule-1
  • Green Fluorescent Proteins