Type I interferon production by tertiary lymphoid tissue developing in response to 2,6,10,14-tetramethyl-pentadecane (pristane)

Am J Pathol. 2006 Apr;168(4):1227-40. doi: 10.2353/ajpath.2006.050125.


Lymphoid neogenesis is associated with antibody-mediated autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. Although systemic lupus erythematosus is the prototypical B-cell-mediated autoimmune disease, the role of lymphoid neogenesis in its pathogenesis is unknown. Intraperitoneal injection of 2,6,10,14-tetramethyl-pentadecane (TMPD, pristane) or mineral oil causes lipogranuloma formation in mice, but only TMPD-treated mice develop lupus. We report that lipogranulomas are a form of lymphoid neogenesis. Immunoperoxidase staining of lipogranulomas revealed B cells, CD4(+) T cells, and dendritic cells and in some cases organization into T- and B-cell zones. Lipogranulomas also expressed the lymphoid chemokines CCL21, CCL19, CXCL13, CXCL12, and CCL22. Expression of the type I interferon (IFN-I)-inducible genes Mx1, IRF7, IP-10, and ISG-15 was greatly increased in TMPD- versus mineral oil-induced lipogranulomas. Dendritic cells from TMPD lipogranulomas underwent activation/maturation with high CD86 and interleukin-12 expression. Magnetic bead depletion of dendritic cells markedly diminished IFN-inducible gene (Mx1) expression. We conclude that TMPD-induced lupus is associated with the formation of ectopic lymphoid tissue containing activated dendritic cells producing IFN-I and interleukin-12. In view of the increased IFN-I production in systemic lupus erythematosus, these studies suggest that IFN-I from ectopic lymphoid tissue could play a role in the pathogenesis of experimental lupus in mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chemokine CXCL10
  • Chemokines / biosynthesis
  • Chemokines, CXC / biosynthesis
  • Choristoma / chemically induced
  • Choristoma / metabolism
  • Choristoma / pathology
  • Cytokines / biosynthesis
  • Dendritic Cells / metabolism
  • Female
  • GTP-Binding Proteins / biosynthesis
  • Granuloma / chemically induced
  • Granuloma / metabolism*
  • Granuloma / pathology
  • Interferon Regulatory Factor-7 / biosynthesis
  • Interferon Type I / biosynthesis*
  • Interleukin-12 / biosynthesis
  • Lupus Erythematosus, Systemic / chemically induced
  • Lupus Erythematosus, Systemic / pathology
  • Lymphoid Tissue / drug effects
  • Lymphoid Tissue / metabolism*
  • Lymphoid Tissue / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mineral Oil
  • Myxovirus Resistance Proteins
  • Peritoneum
  • Terpenes*
  • Ubiquitins / biosynthesis


  • Chemokine CXCL10
  • Chemokines
  • Chemokines, CXC
  • Cytokines
  • G1p2 protein, mouse
  • Interferon Regulatory Factor-7
  • Interferon Type I
  • Irf7 protein, mouse
  • Mx1 protein, mouse
  • Myxovirus Resistance Proteins
  • Terpenes
  • Ubiquitins
  • Interleukin-12
  • pristane
  • Mineral Oil
  • GTP-Binding Proteins