Cutting edge: lupus susceptibility interval Sle3/5 confers responsiveness to prolactin in C57BL/6 mice.

Abstract

Prolactin is of interest in the pathogenesis of systemic lupus erythematosus (SLE) because almost 25% of SLE patients display hyperprolactinemia, and serum prolactin correlates with disease activity in some patients. Furthermore, hyperprolactinemia causes early mortality in lupus-prone mice and induces a lupus-like phenotype in nonspontaneously autoimmune mice. We show here that the immunomodulatory effects of prolactin are genetically determined; hyperprolactinemia breaks B cell tolerance and causes a lupus-like serology in BALB/c mice expressing a transgene encoding the H chain of an anti-DNA Ab but not in C57BL/6 transgenic mice. In C57BL/6 mice that express both the H chain transgene and the lupus susceptibility interval Sle3/5, prolactin induces increased serum titers of anti-DNA Ab and glomerular Ig depositions. The increase in costimulation due to prolactin-mediated up-regulation of both CD40 on B cells and CD40L on T cells would appear to play a central role in lupus induction in this model.

• Authors: Elena Peeva, Juana Gonzalez, Ruthmarie Hicks, Betty Diamond
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 177 Issue 3 Pg. 1401-5 (Aug 01 2006) ISSN: 0022-1767 [Print] United States
• PMID: 16849443 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• CD40 Antigens
• CD40 Ligand
• Prolactin

Topics

• Administration, Cutaneous
• Animals
• Apoptosis (genetics, immunology)
• B-Lymphocytes (cytology, immunology, metabolism)
• CD4-CD8 Ratio
• CD4-Positive T-Lymphocytes (immunology)
• CD40 Antigens (biosynthesis)
• CD40 Ligand (biosynthesis)
• Cell Differentiation (genetics, immunology)
• Female
• Genetic Predisposition to Disease
• Lupus Erythematosus, Systemic (genetics, immunology, pathology)
• Lymphocyte Activation
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred NZB
• Mice, Transgenic
• Prolactin (administration & dosage, blood, physiology)
• Up-Regulation (genetics, immunology)