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

Abstract

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.

• Authors: Dina C Nacionales, Kindra M Kelly, Pui Y Lee, Haoyang Zhuang, Yi Li, Jason S Weinstein, Eric Sobel, Yoshiki Kuroda, Jun Akaogi, Minoru Satoh, Westley H Reeves
• Journal: The American journal of pathology (Am J Pathol) Vol. 168 Issue 4 Pg. 1227-40 (Apr 2006) ISSN: 0002-9440 [Print] United States
• PMID: 16565497 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

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